do not experiment on animals

Should Animals Be Used for Scientific or Commercial Testing?

• History of Animal Testing

Animals are used to develop medical treatments, determine the toxicity of medications, check the safety of products destined for human use, and other  biomedical , commercial, and health care uses. Research on living animals has been practiced since at least 500 BC.

Descriptions of the dissection of live animals have been found in ancient Greek writings from as early as circa 500 BC. Physician-scientists such as  Aristotle ,  Herophilus , and  Erasistratus  performed the experiments to discover the functions of living organisms.  Vivisection  (dissection of a living organism) was practiced on human criminals in ancient Rome and Alexandria, but prohibitions against mutilation of the human body in ancient Greece led to a reliance on animal subjects. Aristotle believed that animals lacked intelligence, and so the notions of justice and injustice did not apply to them.  Theophrastus , a successor to Aristotle, disagreed, objecting to the vivisection of animals on the grounds that, like humans, they can feel pain, and causing pain to animals was an affront to the gods. Read more background…

Pro & Con Arguments

Pro 1 Animal testing contributes to life-saving cures and treatments for humans and animals alike. Nearly every medical breakthrough in the last 100 years has resulted directly from research using animals, according to the California Biomedical Research Association. To name just a few examples, animal research has contributed to major advances in treating conditions including breast cancer, brain injury, childhood leukemia, cystic fibrosis, multiple sclerosis, and tuberculosis. Testing on animals was also instrumental in the development of pacemakers, cardiac valve substitutes, and anesthetics. [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] Scientists racing to develop a vaccine for coronavirus during the 2020 global pandemic needed to test on genetically modified mice to ensure that the vaccine did not make the virus worse. Nikolai Petrovsky, professor in the College of Medicine and Public Health at Flinders University in Australia, said testing a coronavirus vaccine on animals is “absolutely essential” and skipping that step would be “fraught with difficulty and danger.” [ 119 ] [ 133 ] Researchers have to test extensively to prevent “vaccine enhancement,” a situation in which a vaccine actually makes the disease worse in some people. “The way you reduce that risk is first you show it does not occur in laboratory animals,” explains Peter Hotez, Dean for the National School of Tropical Medicine at Baylor College. [ 119 ] [ 141 ] Further, animals themselves benefit from the results of animal testing. Vaccines tested on animals have saved millions of animals that would otherwise have died from rabies, distemper, feline leukemia, infectious hepatitis virus, tetanus, anthrax, and canine parvo virus. Treatments for animals developed using animal testing also include pacemakers for heart disease and remedies for glaucoma and hip dysplasia. [ 9 ] [ 21 ] Animal testing has also been instrumental in saving endangered species from extinction, including the black-footed ferret, the California condor and the tamarins of Brazil. The American Veterinary Medical Association (AVMA) endorses animal testing to develop safe drugs, vaccines, and medical devices. [ 9 ] [ 13 ] [ 23 ] Read More

Pro 2 Animals are appropriate research subjects because they are similar to human beings in many ways. Chimpanzees share 99% of their DNA with humans, and mice are 98% genetically similar to humans. All mammals, including humans, are descended from common ancestors, and all have the same set of organs (heart, kidneys, lungs, etc.) that function in essentially the same way with the help of a bloodstream and central nervous system. Because animals and humans are so biologically similar, they are susceptible to many of the same conditions and illnesses, including heart disease, cancer, and diabetes. [ 9 ] [ 17 ] [ 18 ] Animals often make better research subjects than humans because of their shorter life cycles. Laboratory mice, for example, live for only two to three years, so researchers can study the effects of treatments or genetic manipulation over a whole lifespan, or across several generations, which would be infeasible using human subjects. Mice and rats are particularly well-suited to long-term cancer research, partly because of their short lifespans. [ 9 ] [ 29 ] [ 30 ] Further, animals must be used in cases when ethical considerations prevent the use of human subjects. When testing medicines for potential toxicity, the lives of human volunteers should not be put in danger unnecessarily. It would be unethical to perform invasive experimental procedures on human beings before the methods have been tested on animals, and some experiments involve genetic manipulation that would be unacceptable to impose on human subjects before animal testing. The World Medical Association Declaration of Helsinki states that human trials should be preceded by tests on animals. [ 19 ] [ 20 ] A poll of 3,748 scientists by the Pew Research Center found that 89% favored the use of animals in scientific research. The American Cancer Society, American Physiological Society, National Association for Biomedical Research, American Heart Association, and the Society of Toxicology all advocate the use of animals in scientific research. [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ] [ 120 ] Read More

Pro 3 Animal research is highly regulated, with laws in place to protect animals from mistreatment. In addition to local and state laws and guidelines, animal research has been regulated by the federal Animal Welfare Act (AWA) since 1966. As well as stipulating minimum housing standards for research animals (enclosure size, temperature, access to clean food and water, and others), the AWA also requires regular inspections by veterinarians. [ 3 ] All proposals to use animals for research must be approved by an Institutional Animal Care and Use Committee (IACUC) set up by each research facility. Most major research institutions’ programs are voluntarily reviewed for humane practices by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). [ 24 ] [ 25 ] Animal researchers treat animals humanely, both for the animals’ sake and to ensure reliable test results. Research animals are cared for by veterinarians, husbandry specialists, and animal health technicians to ensure their well-being and more accurate findings. Rachel Rubino, attending veterinarian and director of the animal facility at Cold Springs Harbor Laboratory, says, “Most people who work with research animals love those animals…. We want to give them the best lives possible, treat them humanely.” At Cedars-Sinai Medical Center’s animal research facility, dogs are given exercise breaks twice daily to socialize with their caretakers and other dogs, and a “toy rotation program” provides opportunities for play. [ 28 ] [ 32 ] Read More

Con 1 Animal testing is cruel and inhumane. Animals used in experiments are commonly subjected to force feeding, food and water deprivation, the infliction of burns and other wounds to study the healing process, the infliction of pain to study its effects and remedies, and “killing by carbon dioxide asphyxiation, neck-breaking, decapitation, or other means,” according to Humane Society International. The US Department of Agriculture reported in Jan. 2020 that research facilities used over 300,000 animals in activities involving pain in just one year. [ 47 ] [ 102 ] Plus, most experiments involving animals are flawed, wasting the lives of the animal subjects. A peer-reviewed study found serious flaws in the majority of publicly funded US and UK animal studies using rodents and primates: “only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used.” A 2017 study found further flaws in animal studies, including “incorrect data interpretation, unforeseen technical issues, incorrectly constituted (or absent) control groups, selective data reporting, inadequate or varying software systems, and blatant fraud.” [ 64 ] [ 128 ] Only 5% of animals used in experiments are protected by US law. The Animal Welfare Act (AWA) does not apply to rats, mice, fish, and birds, which account for 95% of the animals used in research. The types of animals covered by the AWA account for fewer than one million animals used in research facilities each year, which leaves around 25 million other animals without protection from mistreatment. The US Department of Agriculture, which inspects facilities for AWA compliance, compiles annual statistics on animal testing but they only include data on the small percentage of animals subject to the Act. [ 1 ] [ 2 ] [ 26 ] [ 28 ] [ 135 ] Even the animals protected by the AWA are mistreated. Violations of the Animal Welfare Act at the federally funded New Iberia Research Center (NIRC) in Louisiana included maltreatment of primates who were suffering such severe psychological stress that they engaged in self-mutilation, infant primates awake and alert during painful experiments, and chimpanzees being intimidated and shot with a dart gun. [ 68 ] Read More

Con 2 Animal tests do not reliably predict results in human beings. 94% of drugs that pass animal tests fail in human clinical trials. Over 100 stroke drugs and over 85 HIV vaccines failed in humans after succeeding in animal trials. Nearly 150 clinical trials (human tests) of treatments to reduce inflammation in critically ill patients have been undertaken, and all of them failed, despite being successful in animal tests. [ 57 ] [ 58 ] [ 59 ] Drugs that pass animal tests are not necessarily safe. The 1950s sleeping pill thalidomide, which caused 10,000 babies to be born with severe deformities, was tested on animals prior to its commercial release. Later tests on pregnant mice, rats, guinea pigs, cats, and hamsters did not result in birth defects unless the drug was administered at extremely high doses. Animal tests on the arthritis drug Vioxx showed that it had a protective effect on the hearts of mice, yet the drug went on to cause more than 27,000 heart attacks and sudden cardiac deaths before being pulled from the market. [ 5 ] [ 55 ] [ 56 ] [ 109 ] [ 110 ] Plus, animal tests may mislead researchers into ignoring potential cures and treatments. Some chemicals that are ineffective on (or harmful to) animals prove valuable when used by humans. Aspirin, for example, is dangerous for some animal species. Intravenous vitamin C has shown to be effective in treating sepsis in humans, but makes no difference to mice. Fk-506 (tacrolimus), used to lower the risk of organ transplant rejection, was “almost shelved” because of animal test results, according to neurologist Aysha Akhtar. A report on Slate.com stated that a “source of human suffering may be the dozens of promising drugs that get shelved when they cause problems in animals that may not be relevant for humans.” [ 105 ] [ 106 ] [ 127 ] Read More

Con 3 Alternative testing methods now exist that can replace the need for animals. Other research methods such as in vitro testing (tests done on human cells or tissue in a petri dish) offer opportunities to reduce or replace animal testing. Technological advancements in 3D printing allow the possibility for tissue bioprinting: a French company is working to bioprint a liver that can test the toxicity of a drug. Artificial human skin, such as the commercially available products EpiDerm and ThinCert, can be made from sheets of human skin cells grown in test tubes or plastic wells and may produce more useful results than testing chemicals on animal skin. [ 15 ] [ 16 ] [ 50 ] [ 51 ] Michael Bachelor, Senior Scientist and Product Manager at biotech company MatTek, stated, “We can now create a model from human skin cells — keratinocytes — and produce normal skin or even a model that mimics a skin disease like psoriasis. Or we can use human pigment-producing cells — melanocytes — to create a pigmented skin model that is similar to human skin from different ethnicities. You can’t do that on a mouse or a rabbit.” The Environmental Protection Agency is so confident in alternatives that the agency intends to reduce chemical testing on mammals 30% by 2025 and end it altogether by 2035. [ 61 ] [ 134 ] [ 140 ] Scientists are also able to test vaccines on humans volunteers. Unlike animals used for research, humans are able to give consent to be used in testing and are a viable option when the need arises. The COVID-19 (coronavirus) global pandemic demonstrated that researchers can skip animal testing and go straight to observing how vaccines work in humans. One company working on a COVID-19 vaccine, Moderna Therapeutics, worked on developing a vaccine using new technology: instead of being based on a weakened form of the virus, it was developed using a synthetic copy of the COVID-19 genetic code. [ 142 ] [ 143 ] Read More

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16 Integral Pros and Cons of Animal Experimentation

Over 25 million animals are used for experimentation in the U.S. every year. Monkeys, rabbits, cats, ferrets, pigs, sheep and chimpanzees are just some of the animals used for biomedical experiments, science education, and product and cosmetics testing. Some animals, however, are more preferred by laboratories. In fact, over 90% of test subjects are mice, birds and rats.

Many proponents of animal experimentation claim that the process is for a good cause. Better to use animals than humans for testing, right? After all, they are below humans in the natural chain of things. But, as English philosopher and social reformer Jeremy Bentham puts it, it is not a question of whether they can talk or reason, but whether or not they suffer. Considering that animals cry and show discomfort, it is safe to conclude that they feel something.

Unfortunately, vivisection, or the practice of animal experimentation, is perfectly acceptable and legal. It is the worst form of animal abuse that is institutionalized and sanctioned by our society. Despite the fact that the conditions of animals in labs are monotonous, stressful, and very unnatural for them, invasive experimentation persists, and even when the endpoint is death. Whether animal experimentation is good or bad really depends on who you are asking. But, if it is condone by society, then there must be some advantages to it, even if the benefits are at the expense of animal lives.

List of Pros of Animal Experimentation

1. Contributes to many cures and treatments that save many human lives The majority of the medical breakthroughs that have happened in the last 100 years were direct results from animal research and experimentation, according to the California Biomedical Research Association. Insulin, for example, was discovered through an experiment where dogs have their pancreases removed. The Anderson Cancer Center animal research also associated the vaccine for Hepatitis B with experimentation on chimpanzees. Without these experimentations, thousands, if not millions, of diabetic patients and those with hepatitis B would have been killed every year. The same facility also said that the chimps serve as humanity’s only hope for finding a Hepatitis C vaccine.

2. Provides adequate living, whole body system test subject No other living thing in this planet has the closest anatomical structure as humans than animals. A human body is extremely complex that cell cultures in a petri dish cannot provide sufficient test results or proof that a cure or product is effective. Testing a drug for side effects, for example, requires a circulatory system that will carry the drug to different organs. Studying interrelated processes is also best done in subjects with endocrine system, immune system, and central nervous system, something humans and animals have. What about the use of computer models? They would require accurate information that is gathered from animal research.

3. Humans and animals are almost identical in many ways The DNA of chimpanzees are 99% similar with humans, while the genetics of mice are 98% similar. Humans and animals are also biologically similar, having the same set of organs, bloodstream and central nervous system, which is why they are affected with the same diseases and health conditions. Given these circumstances, animals used in experimentation do serve as appropriate research subjects.

4. Provides an ethical alternative for testing Most people would say that it is unethical to use humans for invasive experimental procedures, especially when it can result in death. The lives of human volunteers must not be endangered when testing medicines for side effects or potential toxicity. Ethical consideration must also be made when genetic manipulation would be involved. Human trials must be preceded by animal testing, as stated by the World Medical Association Declaration of Helsinki. But, if animals could talk, they would probably demand the same ethical considerations.

5. Offer benefits to animals themselves Animal experimentation is not only beneficial to humans but animals as well. If the vaccines were not tested on them, a lot of them could have died from rabies, infectious hepatitis virus, anthrax, feline leukemia, and canine parvovirus. Remedies for hip dysplasia and glaucoma were also discovered through animal testing. But the real highlight is that vivisection helped kept endangered species, such as the California condor, the tamarins of Brazil, and the black-footed ferret, from becoming extinct. This is why animal testing is endorsed by the American Veterinary Medical Association.

6. Allow researchers to study a test subject for a whole life span Humans can live up to 80 years or more, which means some scientists would be dead before others results will be gathered. Laboratory mice, on the other hand, only live for 2 to 3 years, giving researchers an opportunity to study effects of genetic manipulation or treatments over an entire lifetime. In some cases, they can continue to study across several generations. This is why mice and rats have been used for long-term cancer research.

7. Animals are protected from abuse and mistreatment Contrary to what most opponents believe, animal research is highly regulated, with laws enacted to protect animals. Since 1966, the federal Animal Welfare Act have been regulating animal experimentation.

• Research animals must be provided with shelter that follows minimum housing standards, such as the right-sized enclosure, recommended temperature, access to clean food and water, etc.
• Veterinarians must regularly inspect the animals and their living conditions
• Each research facility must set up an Institutional Animal Care and Use Committee (IACUC) that will approve all proposals to use animals for experimentation.
• The IACUC will be responsible for enforcing humane treatment of animals.
• Research facilities funded by the US Public Health Service (PHS) must comply with the policies on Human Care and Use of Laboratory Animals imposed by PHS.

8. Fewer animals are used in research than as food for humans Compared to the amount of chicken, cattle, sheep and pigs that humans eat, relatively few of them are used in experimentation. With consideration to the medical progress and advancement such tests provided, it is a small price to pay. To illustrate, for every chicken used in research, an equivalent of 340 are used as food.

List of Cons of Animal Experimentation

1. Cruel and inhumane treatment Protocols in animal testing are often painful to the test subjects. They are forced fed, deprived of food and water, restrained physically for prolonged periods, inflicted with burns, wounds and pain to test for healing process effects and remedies, and even killed through neck-breaking or asphyxiation. This is according to the Humane Society International. When testing to evaluate irritation caused by cosmetics, for example, a rabbit’s eyes will be held open by clips so it cannot blink away the products being evaluated. The clips usually stay on for days, and to ensure the rabbits stay in place, they are incapacitated. Some experimentation also involves using lethal doses of certain chemicals to determine how much can kill animals.

2. Animals make poor test subjects This statement is a direct contradiction from what proponents believe about how closely related animals and humans are anatomically and biologically, because of the many metabolic, cellular, and anatomical differences between the two species. Using rats for toxicity, for example, must not be accepted as reliable since humans are nowhere close to being 70-kilogram rats, according to Thomas Hartung, professor of evidence-based toxicology at Johns Hopkins University. This is further supported by the 2013 study in the Archives of Toxicology that states that the lack of direct comparison of human data versus that of a mouse makes the usefulness of research data dubious.

3. Success in animal experimentation does not equate to human safety When the sleeping pill thalidomide was tested on pregnant rats, mice, cats and guinea pigs, there were no incidence of birth defects, except when administered at extremely high doses. However, when it was used by pregnant women, it resulted in severe deformities affecting 10,000 babies.

• The arthritis drug Vioxx, which turned out great on animals was really bad news on humans because it caused more than 20,000 heart attacks and sudden cardiac deaths.
• A majority of the drugs that passed animal tests, 94% to be exact, failed in human clinical trials.
• 100 of the drugs designed to treat stroke worked on animals, but completely failed in humans
• Over 85 vaccines for HIV worked well in primates, but failed in humans

4. Can lead to misleading research Some medicines and products that are harmful to animals are actually valuable to humans. Aspirin, for example, was almost shelved because it proved dangerous for animals. Imagine what would have happened if aspirin was completely taken off the pharmaceutical list? There would have been no way to lower the risk of organ transplant being rejected.

5. Most animals used in testing and research are not protected by the Animal Welfare Act (AWA) As of 2010, only over 1 million animals are covered by the AWA, leaving around 25 million more unprotected from mistreatment and abuse. These include birds, fish, mice and rats. And because vivisections within laboratory walls are regulated by the committee that the facility itself selected, animal subjects are even more at risk of being treated like prisoners in a hospital for their entire existence. One very good example of a clear violation of AWA was discovered in a federally funded facility in Louisiana, New Iberia Research Center (NIRC). The animals were so stressed out psychologically that they resorted to self-mutilation. The rest of the 337 violations that NIRC committed were caught on a video footage, showing the heartbreaking conditions of the animals. But this facility is just one of the many that violates AWA.

6. There are less expensive alternatives to animal experimentation Despite what proponents insist, cell cultures in a petri dish, or in vitro (in glass) testing, are not exactly useless or insufficient. They can even produce results that are more relevant than animal experimentation. The same thing is true when using artificial human skin as a test subject, instead of animal skin. Virtual reconstructions of human molecular structures done through computer models also have the capacity to predict toxicity levels of substances, so no need to poison animals to collect data and draw conclusions. And, when testing for adverse reactions, administering small doses on humans, also known as microdosing, also offers an alternative. Combined with blood analysis, results will be produced.

But what is really important is that these alternatives are less expensive than animal experimentations. In glass testing, for example, only costs $11,000, which is less than $21,000 than an “unscheduled DNA synthesis”. A phototoxicity test that doesn’t use rats only cost $1,300, which is almost $10,000 less than its animal-based equivalent. These only shows that animal tests are wasting plenty of government dollars allocated for research.

7. Plenty of animal lives are wasted Considering all the tests that failed, not to mention other non-experimental factors that affect animals, there is a significant number of animal lives wasted for nothing. They suffer or get killed during the experiment, and suffer the same fate after the experiment. But what is really inhumane and unethical are the poor research procedures used by some facilities. Serious flaws were discovered in plenty of studies in the UK and the U.S. that use rodents, according to a peer-reviewed study conducted in 2009. Selection bias was a major problem, but even with randomization and blinding technique used, proper selection of animals still failed. There is also a lack of hypothesis or objective related to the study.

8. Medical breakthroughs need not involve animals Is animal experimentation really that necessary in discovering treatments and cures? Opponents argue that there is really no evidence of its vital role in major medical advances. If funds and resources are focused on animal-free alternatives, more humane, ethical and inexpensive solutions. One such alternative that should be given full support is the microfluidic chip, also known as organs on a chip. This involves the use of chips to achieve certain functions of a human body, such as mix, pump and sort. The chips are lined with human cells so they work similar to human organs. With this alternative, researchers can no longer use the excuse that they need a living, whole-body system to run experiments.

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About Animal Testing

Humane Society International / Global

What is animal testing?

The term “animal testing” refers to procedures performed on living animals for purposes of research into basic biology and diseases, assessing the effectiveness of new medicinal products, and testing the human health and/or environmental safety of consumer and industry products such as cosmetics, household cleaners, food additives, pharmaceuticals and industrial/agro-chemicals. All procedures, even those classified as “mild,” have the potential to cause the animals physical as well as psychological distress and suffering. Often the procedures can cause a great deal of suffering. Most animals are killed at the end of an experiment, but some may be re-used in subsequent experiments. Here is a selection of common animal procedures:

• Forced chemical exposure in toxicity testing, which can include oral force-feeding, forced inhalation, skin or injection into the abdomen, muscle, etc.
• Exposure to drugs, chemicals or infectious disease at levels that cause illness, pain and distress, or death
• Genetic manipulation, e.g., addition or “knocking out” of one or more genes
• Ear-notching and tail-clipping for identification
• Short periods of physical restraint for observation or examination
• Prolonged periods of physical restraint
• Food and water deprivation
• Surgical procedures followed by recovery
• Infliction of wounds, burns and other injuries to study healing
• Infliction of pain to study its physiology and treatment
• Behavioural experiments designed to cause distress, e.g., electric shock or forced swimming
• Other manipulations to create “animal models” of human diseases ranging from cancer to stroke to depression
• Killing by carbon dioxide asphyxiation, neck-breaking, decapitation, or other means

What types of animals are used?

Many different species are used around the world, but the most common include mice, fish, rats, rabbits, guinea pigs, hamsters, farm animals, birds, cats, dogs, mini-pigs, and non-human primates (monkeys, and in some countries, chimpanzees). Video: Watch what scientists have to say about alternatives to animal testing .

It is estimated that more than 115 million animals worldwide are used in laboratory experiments every year. But because only a small proportion of countries collect and publish data concerning animal use for testing and research, the precise number is unknown. For example, in the United States, up to 90 percent of the animals used in laboratories (purpose-bred rats, mice and birds, fish, amphibians, reptiles and invertebrates) are excluded from the official statistics, meaning that figures published by the U.S. Department of Agriculture are no doubt a substantial underestimate.

Within the European Union, more than 12 million animals are used each year, with France, Germany and the United Kingdom being the top three animal using countries. British statistics reflect the use of more than 3 million animals each year, but this number does not include animals bred for research but killed as “surplus” without being used for specific experimental procedures. Although these animals still endure the stresses and deprivation of life in the sterile laboratory environment, their lives are not recorded in official statistics. HSI believes that complete transparency about animal use is vital and that all animals bred, used or killed for the research industry should be included in official figures. See some animal use statistics .

What’s wrong with animal testing?

For nearly a century, drug and chemical safety assessments have been based on laboratory testing involving rodents, rabbits, dogs, and other animals. Aside from the ethical issues they pose—inflicting both physical pain as well as psychological distress and suffering on large numbers of sentient creatures—animal tests are time- and resource-intensive, restrictive in the number of substances that can be tested, provide little understanding of how chemicals behave in the body, and in many cases do not correctly predict real-world human reactions. Similarly, health scientists are increasingly questioning the relevance of research aimed at “modelling” human diseases in the laboratory by artificially creating symptoms in other animal species.

Trying to mirror human diseases or toxicity by artificially creating symptoms in mice, dogs or monkeys has major scientific limitations that cannot be overcome. Very often the symptoms and responses to potential treatments seen in other species are dissimilar to those of human patients. As a consequence, nine out of every 10 candidate medicines that appear safe and effective in animal studies fail when given to humans. Drug failures and research that never delivers because of irrelevant animal models not only delay medical progress, but also waste resources and risk the health and safety of volunteers in clinical trials.

What’s the alternative?

If lack of human relevance is the fatal flaw of “animal models,” then a switch to human-relevant research tools is the logical solution. The National Research Council in the United States has expressed its vision of “a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines”, and science leaders around the world have echoed this view.

The sequencing of the human genome and birth of functional genomics, the explosive growth of computer power and computational biology, and high-speed robot automation of cell-based (in vitro) screening systems, to name a few, has sparked a quiet revolution in biology. Together, these innovations have produced new tools and ways of thinking that can help uncover exactly how chemicals and drugs disrupt normal processes in the human body at the level of cells and molecules. From there, scientists can use computers to interpret and integrate this information with data from human and population-level studies. The resulting predictions regarding human safety and risk are potentially more relevant to people in the real world than animal tests.

But that’s just the beginning. The wider field of human health research could benefit from a similar shift in paradigm. Many disease areas have seen little or no progress despite decades of animal research. Some 300 million people currently suffer from asthma, yet only two types of treatment have become available in the last 50 years. More than a thousand potential drugs for stroke have been tested in animals, but only one of these has proved effective in patients. And it’s the same story with many other major human illnesses. A large-scale re-investment in human-based (not mouse or dog or monkey) research aimed at understanding how disruptions of normal human biological functions at the levels of genes, proteins and cell and tissue interactions lead to illness in our species could advance the effective treatment or prevention of many key health-related societal challenges of our time.

Modern non-animal techniques are already reducing and superseding experiments on animals, and in European Union, the “3Rs” principle of replacement, reduction and refinement of animal experiments is a legal requirement. In most other parts of the world there is currently no such legal imperative, leaving scientists free to use animals even where non-animal approaches are available.

If animal testing is so unreliable, why does it continue?

Despite this growing evidence that it is time for a change, effecting that change within a scientific community that has relied for decades on animal models as the “default method” for testing and research takes time and perseverance. Old habits die hard, and globally there is still a lack of knowledge of and expertise in cutting-edge non-animal techniques.

But with HSI’s help, change is happening. We are leading efforts globally to encourage scientists, companies and policy-makers to transition away from animal use in favour of 21st century methods. Our work brings together experts from around the globe to share knowledge and best practice, improving the quality of research by replacing animals in the laboratory.

Are animal experiments needed for medical progress?

It is often argued that because animal experiments have been used for centuries, and medical progress has been made in that time, animal experiments must be necessary. But this is missing the point. History is full of examples of flawed or basic practices and ideas that were once considered state-of-the-art, only to be superseded years later by something far more sophisticated and successful. In the early 1900’s, the Wright brothers’ invention of the airplane was truly innovative for its time, but more than a century later, technology has advanced so much that when compared to the modern jumbo jet those early flying machines seem quaint and even absurd. Those early ideas are part of aviation history, but no-one would seriously argue that they represent the cutting-edge of design or human achievement. So it is with laboratory research. Animal experiments are part of medical history, but history is where they belong. Compared to today’s potential to understand the basis of human disease at cellular and molecular levels, experimenting on live animals seems positively primitive. So if we want better quality medical research, safer more effective pharmaceuticals and cures to human diseases, we need to turn the page in the history books and embrace the new chapter—21st century science.

Independent scientific reviews demonstrate that research using animals correlates very poorly to real human patients. In fact, the data show that animal studies fail to predict real human outcomes in 50 to 99.7 percent of cases. This is mainly because other species seldom naturally suffer from the same diseases as found in humans. Animal experiments rely on often uniquely human conditions being artificially induced in non-human species. While on a superficial level they may share similar symptoms, fundamental differences in genetics, physiology and biochemistry can result in wildly different reactions to both the illness and potential treatments. For some areas of disease research, overreliance on animal models may well have delayed medical progress rather than advanced it. By contrast, many non-animal replacement methods such as cell-based studies, silicon chip biosensors, and computational systems biology models, can provide faster and more human-relevant answers to medical and chemical safety questions that animal experiments cannot match.

“The claim that animal experimentation is essential to medical development is not supported by proper, scientific evidence but by opinion and anecdote. Systematic reviews of its effectiveness don’t support the claims made on its behalf” (Pandora Pound et al. British Medical Journal 328, 514-7, 2004).

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Imagine a syringe being forced down your throat to inject a chemical into your stomach, or being restrained and forced to breathe sickening vapours for hours. That’s the cruel reality of animal testing for millions of mice, rabbits, dogs and other animals worldwide.

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We all dream of the day when cancer is cured and AIDS is eradicated, but is the continued use of mice, monkeys and other animals as experimental “models” of human disease actually holding us back from realizing the promise of 21st century science?

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Animal testing and experiments FAQ

How many animals are used in experiments each year?

Which animals are used in experiments, what kinds of experiments are animals used in, what kinds of institutions use animals in experiments, where do laboratories get the animals they use in experiments, what is life like for animals in laboratories, what happens to the animals once an experiment is over, aren’t there laws to protect animals used in experiments, why are animals still used in experiments, what are the alternatives to experiments on animals, what are the advantages of using non-animal alternatives instead of animals in experiments.

• What are you doing to end experiments on animals?

What can I do to help animals in laboratories?

Stand with us to demand that the federal government, state governments, companies and universities stop relying on outdated animal experiments.

It is estimated that more than 50 million animals are used in experiments each year in the United States. Unfortunately, no accurate figures are available to determine precisely how many animals are used in experiments in the U.S. or worldwide.

The U.S. Department of Agriculture (USDA) does compile annual statistics on some animals used in experiments, including cats , dogs , guinea pigs , hamsters , pigs , primates , rabbits and  sheep .

However, the animals most commonly used in experiments—“purpose-bred” mice and rats  (mice and rats bred specifically to be used in experiments)—are not counted in annual USDA statistics and are not afforded the minimal protections provided by the Animal Welfare Act. The Animal Welfare Act is a federal law that sets minimal standards for the treatment of certain warm-blooded animals used in experiments. The law also requires that unannounced inspections of all regulated animal testing facilities are carried out annually, although some facilities only receive partial inspections . In addition to purpose-bred mice and rats, animals such as crabs, fish , frogs, octopuses and turtles , as well as purpose-bred birds , are not covered by the Animal Welfare Act. The failure to protect these animals under the law means that there is no oversight or scrutiny of their treatment in the laboratory or the experiments performed on them. And, because these animals are not counted, no one knows how many of them are suffering in laboratories. It also means that facilities using unprotected species in experiments are not required to search for alternative, non-animal methods that could be used to replace or reduce harmful experiments that use animals.

View Animals Used in Experiments by State

View Dogs Used in Experiments by State

Read Dogs Used in Experiments FAQ

Use our Animal Laboratory Search Tool  to find information about universities, hospitals, companies and other organizations that use certain animals in experiments

View a list of U.S. laboratories that use certain animals in experiments ; click on “License Type” and select “Class R – Research Facilities." Note that numbers only include animals covered by the Animal Welfare Act.

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Animals used in experiments include baboons, cats , cows , dogs , ferrets,  fish , frogs, guinea pigs , hamsters , horses , llamas, mice , monkeys (such as marmosets and macaques), owls, pigs , quail, rabbits , rats and  sheep .

Chimpanzees have thankfully not been subjected to invasive experiments in the U.S. since 2015, when federal decisions were made to prevent their use. Despite this, hundreds of chimpanzees are still languishing in laboratories while they wait to be moved to sanctuaries.

Animals are used in many different kinds of experiments. These are just a few examples:

• Dogs have their hearts, lungs or kidneys deliberately damaged or removed to study how experimental substances might affect human organ function.  
• Monkeys are taken from their mothers as infants to study how extreme stress might affect human behavior.
• Mice are force-fed daily doses of a chemical for two years to see if it might cause cancer in humans.
• Cats have their spinal cords damaged and are forced to run on treadmills to study how nerve activity might affect human limb movement.
• Ferrets are deliberately infected with extremely painful, potentially fatal diseases (such as RSV, COVID-19 or Ebola) and not given pain relief or treatment before their death to study how humans might be affected by the same disease.  
• Pigs are implanted with various devices (such as pacemakers and dental implants) to study how human bodies might respond to such devices.  
• Pregnant rabbits are force-fed toxic pesticides every day for several weeks to study how human mothers and babies might be affected if they were exposed to the pesticides.
• Sheep are subjected to high pressures (such as those experienced deep underwater) for hours at a time and then returned to normal pressure so that their response can be observed.
• Rats are placed in small tubes and are forced to inhale cigarette smoke for hours at a time to study how humans might respond to cigarette smoke.   
• Baboons are injected with endometrial tissue to induce painful symptoms of endometriosis and study how humans might be affected by the disorder.
• Horses are infected with a potentially fatal virus (such as hepatitis) and their symptoms monitored to study how humans might be affected by the same virus.

Experiments are often excruciatingly painful for the animals used and can vary in duration from days to months to years. The experiment can cause vomiting, diarrhea, irritation, rashes, bleeding, loss of appetite, weight loss, convulsions, respiratory distress, salivation, paralysis, lethargy, bleeding, organ abnormalities, tumors, heart failure, liver disease, cancer and death.

There is no limit to the extent of pain and suffering that can be inflicted on animals during experiments. In some instances, animals are not given any kind of pain medication to help relieve their suffering or distress during or after the experiment on the basis that it could affect the experiment.

Animals are typically killed once an experiment is over so that their tissues and organs can be examined, although it is not unusual for animals to be used in multiple experiments over many years. There are no accurate statistics available on how many animals are killed in laboratories every year.

Read Cosmetics Animal Testing FAQ

• Read about our 2022 undercover investigation at Indiana laboratory Inotiv, one of America’s largest animal testing labs. We documented hundreds of dogs, monkeys, rats and pigs undergoing experiments, including terrified beagle puppies being force-fed a potentially toxic drug in cruel and ineffective months-long tests paid for by Crinetics, a pharmaceutical company in San Diego.
• Read about our 2019 undercover investigation at a Michigan laboratory where thousands of dogs are killed every year. After weeks of pressure from the public, the pesticide company that had commissioned a year-long fungicide test on 32 dogs agreed that the test was unnecessary and released the dogs to one of our shelter partners to be adopted.

Chemical, pesticide and drug companies (as well as contract laboratories that carry out tests for those companies), public and private universities, community and technical schools, government facilities, Veterans Affairs (VA) facilities and hospitals all use animals in experiments.

View USDA List of Organizations that Use Dogs in Experiments

View Chart of Institutions That Use Dogs in Experiments

The majority of animals in laboratories are “purpose-bred” meaning that they are bred specifically to be used in experiments. People who breed and sell certain purpose-bred animals are called Class A dealers and are licensed and inspected by the U.S. Department of Agriculture (USDA). Facilities that only sell purpose-bred mice, rats, birds or cold-blooded animals such as crabs, fish, frogs, octopuses and turtles to laboratories are excluded and are not licensed or inspected by the USDA.

Some animals used in experiments are taken from the wild—including birds and  monkeys . 

Historically, some cats and dogs  were sold to laboratories by brokers known as random source Class B dealers, who acquired animals at auctions, from newspaper ads and various other sources, including animal shelters. Random source Class B dealers have not been allowed to operate since 2015 when Congress first passed legislation to prevent them from being licensed.  

Some cats and dogs in laboratories are still obtained directly from animal shelters, a practice known as “pound seizure.” Pound seizure laws vary from state to state with one state (Oklahoma) requiring shelters to give cats and dogs to laboratories, rather than euthanizing them, and others allowing or prohibiting laboratories from taking animals from animal shelters. Some states have no laws at all, leaving it up to the individual shelter or locality.

View Pound Seizure Laws by State

Animals in laboratories suffer immensely. In addition to the painful experiments that the vast majority of animals in laboratories experience over days, months, years or even decades, life in a laboratory is typically a miserable and terrifying experience.

Typically kept alone in barren steel cages with little room to move around and few, if any, comforts, such as toys or soft bedding, animals often become excruciatingly lonelyand anxious, often devoid of the companionship of other animals or the loving touch of a human. Animals in laboratories can associate humans with painful situations and, with no way to hide or get away, they panic whenever a person approaches their cage or freeze with fear when they are taken into treatment rooms. Despite this, dogswill often still seek out human attention.

Animals in laboratories typically also have to watch (or hear) other animals suffering, including their own parents, siblings or babies. High levels of constant stress can cause animals to exhibit unnatural behaviors. For example, it is not uncommon for monkeys to mutilate themselves or to rock or vocalize constantly as a way to help relieve their anxiety, mice to overgroom each other until they are completely bald, and dogs to continually pace.  

Very often the experiments themselves lead to suffering and death. In our 2022 undercover investigation we documented monkeys in “restraint chairs”—devices that are used to hold monkeys in place while the experiments are carried out—who accidentally hanged themselves while unattended. We also documented a dog named Riley used to test a substance so toxic that it brought him near death after only two days of forced dosing. He was hypersalivating, trembling, vomiting, and moaning, yet was dosed yet again with this highly toxic substance. Later, he lay on the floor, unable to stand. Our undercover investigator tried to comfort him while he was dying, but Riley was left to suffer in excruciating pain overnight because the laboratory’s veterinarian was unavailable on a weekend

Animals in laboratories are also subject to mistreatment by inexperienced or careless staff. Although there are penalties for laboratories when animals are injured or killed due to negligence or when they fail to meet minimum standards of animal care, in reality, the fines are typically either very small or waived entirely.

In some cases, animals die as a deliberate result of the experiment. For example, the LD50 (lethal dose 50%) test, which is typically performed on mice, rats, pigeons, quail and fish, involves determining the dose of a substance (such as a pesticide) that kills (or would lead to the death of) 50% of the animals tested.

It is extremely rare that animals are either adopted out or placed into a sanctuary after research is conducted on them. However, more and more states are passing laws that require laboratories, when possible, to offer dogs and cats to shelters and other rescue organizations so they can be adopted into loving homes after the experiments they were used in have ended. As of December 2023, 16 states have such laws.

The Animal Welfare Act was designed to protect certain animals, like dogs and monkeys, used in experiments, but the law only offers minimal standards for housing, food and exercise. The Animal Welfare Act also stipulates that the proposed experiments be reviewed by an Institutional Animal Care and Use Committee, whose members are appointed by the laboratory itself and largely made up of employees of the institution. A 2014 audit report reviewing Animal Welfare Act oversight of laboratories found that “animals are not always receiving basic humane care and treatment and, in some cases, pain and distress are not minimized during and after experimental procedures.”

The animals most commonly used in experiments—“purpose-bred” mice and rats  (mice and rats bred specifically to be used in experiments)—are not counted in annual USDA statistics and are not afforded the minimal protections provided under the Animal Welfare Act. The Animal Welfare Act is a federal law that sets minimal standards for the treatment of certain warm-blooded animals used in experiments. The law also requires that unannounced inspections of all regulated research facilities are carried out annually. In addition to purpose-bred mice and rats, animals such as crabs, fish , frogs, octopuses and turtles as well as purpose-bred birds are not covered by the Animal Welfare Act. The failure to protect these animals under the law means that there is no oversight or scrutiny of their treatment and use in the laboratory. And, because these animals are not counted, no one knows how many of them are suffering in laboratories. It also means that facilities using unprotected species in experiments are not required to search for alternative, non-animal methods that could be used to replace or reduce harmful experiments that use animals.

The vast majority of experiments on animals are not required by government law or regulations. Despite that, government agencies often seem to prefer that companies carry out animal tests to assess the toxicity or efficacy of products such as industrial chemicals, pesticides, medical devices and medicines.

For example, the Environmental Protection Agency (EPA) requires that a new pesticide be fed to dogs for 90 days as part of its evaluation and approval process. The Food and Drug Administration (FDA), which regulates various products such as drugs, medical devices, food, fragrances and color additives, will not approve potential drugs unless they are first tested on animals, which usually includes dogs. In addition to tests on  dogs ,  mice and rats ,  rabbits ,  birds  and primates are also used to test pesticides and drugs. These types of tests have been performed for years, regardless of whether they provide valuable information. While some regulatory agencies, like the EPA, are now taking a critical look at these animal tests to determine if they provide information necessary for assessing how safe a product or substance is for humans, and if better approaches are available, others have done little. More efforts can be made by agencies to invest in and encourage the development of non-animal methods.

Swapping animal experiments for non-animal alternative methods seems like a straightforward process, given that using animals has so many limitations and sophisticated new technologies offer countless possibilities for creating methods that are more humane and that more accurately mimic how the human body will respond to drugs, chemicals or treatments. Unfortunately, developing these alternatives is a complex process facing many obstacles, including inadequate funding. In most cases, a non-animal alternative must be formally validated—historically an expensive and lengthy process—in order to be accepted by government regulatory agencies, both in the U.S. and globally, although new, faster approaches to approving these methods are being developed. In contrast, animal experiments have never been subjected to the same level of scrutiny and validation. Despite these challenges, many scientists are increasingly committed to developing and using non-animal methods.

The world is continuously moving toward a future dominated by sophisticated methods that use human cells, tissues and organs, 3D printing, robotics, computer models and other technologies to create experiments that do not rely on animals.

While many animal experiments have not changed since they were developed decades ago and will always have severe limitations, advanced non-animal methods represent the very latest techniques that science has to offer, provide countless possibilities to improve our understanding and treatment of human diseases and will only continue to improve over time. Non-animal methods also have several advantages over outdated animal experiments: they more closely mimic how the human body responds to drugs, chemicals and treatments; they are more efficient and often less expensive; and they are more humane. Ultimately, moving away from animal experiments is better for both humans and animals.

We advocate for the immediate replacement of animal experiments with available non-animal methods and for more funding to develop new non-animal methods. A concerted effort to shift funding and technological development toward more non-animal alternatives will lead us to a future where animal experiments are a thing of the past.

Examples of non-animal alternative methods

• “Organs-on-chips” are tiny 3D chips created from human cells that look and function like miniature human organs. Organs-on-chips are used to determine how human systems respond to different drugs or chemicals and to find out exactly what happens during infection or disease. Several organs, representing heart, liver, lungs or kidneys, for example, can be linked together through a “microfluidic” circulatory system to create an integrated “human-on-a-chip” model that lets researchers assess multi-organ responses.
• Sophisticated computer models use existing information (instead of carrying out more animal tests) to predict how a medicine or chemical, such as drain cleaner or lawn fertilizer, might affect a human.
• Cells from a cancer patient’s tumor are used to test different drugs and dosages to get exactly the right treatment for that specific individual, rather than testing the drugs on animals.
• Specialized computers use human cells to print 3D tissues that are used to test drugs.
• Skin cells from patients, such as those with Alzheimer’s disease, are turned into other types of cells (brain, heart, lung, etc.) in the laboratory and used to test new treatments.
• Sophisticated computer programming, combined with 3D imaging, is used to develop highly accurate 3D models of human organs, such as the heart. Researchers then input real-world data from healthy people and those with heart disease to make the model hearts “beat” and test how they might respond to new drugs.

Human cells or synthetic alternatives can replace horseshoe crab blood in tests to determine whether bacterial contaminants are present in vaccines or injectable drugs.

• Animal experiments are time-consuming and expensive.
• Animal experiments don’t accurately mimic how the human body and human diseases respond to drugs, chemicals or treatments.
• Animals are very different from humans and, therefore, react differently.
• Increasing numbers of people find animal testing unethical.
• There are many diseases that humans get that animals do not.

What are you doing to end experiments on animals?

We advocate for replacing animals with non-animal alternative methods when they are available and more funding for the development of new alternative methods to quickly replace antiquated and unreliable animal tests and experiments. Our two main areas of focus are ending cosmetics animal testing  and ending experiments on dogs .

Cosmetics testing on animals

We—along with our partner, Humane Society International —are committed to ending cosmetics animal testing forever. Through our  Be Cruelty-Free campaign, we are working in the United States and around the globe to create a world where animals no longer have to suffer to produce lipstick and shampoo. 

• In the United States, we are working to pass the Humane Cosmetics Act , federal legislation that would prohibit animal testing for cosmetics, as well as the sale of animal-tested cosmetics.
• We are also working in several U.S. states to pass legislation that would end cosmetics animal testing. As of March 2024, 12 states (California, Hawai'i, Illinois, Louisiana, Maine, Maryland, Nevada, New Jersey, New York, Oregon, Virginia and Washington) have passed laws banning the sale of animal-tested cosmetics.
• Internationally, as of December 2023, 45 countries have passed laws or regulations to ban cosmetics animal testing, including every country in the European Union, Australia, Brazil, Canada, Chile, Colombia, Ecuador, Guatemala, Iceland, India, Israel, Mexico, New Zealand, Norway, South Korea, Switzerland, Taiwan, Turkey, the United Kingdom.
• We work with scientists from universities, private companies and government agencies around the globe to promote the development, use and regulatory acceptance of non-animal test methods that will reach beyond cosmetics.
• We educate consumers about animals used in cruel and unnecessary cosmetics tests and how to shop for cruelty-free cosmetics and personal care products.

Experiments on dogs

There is no place for harmful experiments on dogs in the U.S. We are committed to ending this practice.

• In the summer of 2022, we led the removal of 3,776 beagles from Envigo, a facility in Virginia that bred dogs to sell to animal laboratories. This historic mission was the result of a lawsuit filed by the U.S. Department of Justice that described shocking violations of the Animal Welfare Act at the facility. Instead of continuing to suffer, the dogs were removed from Envigo and headed to loving homes , a process facilitated by our shelter and rescue partners around the country.
• In April 2022, we released the results of our undercover investigation at Inotiv, an Indiana laboratory where thousands of dogs, monkeys, pigs and rats are used in experiments and killed.
• In 2021, we released a report examining the U.S. government’s role in using dogs in experiments. We found that the government uses millions of taxpayer dollars to fund harmful experiments on dogs each year—and also seems to prefer that companies carry out dog tests. Our researchers scrutinized public records and found that between 2015 and 2019, the National Institutes of Health (NIH) awarded more than $200 million to 200 institutions for 303 projects that used dogs in harmful experiments. Dogs were subjected to multiple surgeries, fitted with equipment to impair their heart function and implanted with devices to alter normal bodily functions. Following the conclusion of an experiment, dogs are typically killed instead of being adopted into loving homes.
• In 2019, we released the results of our undercover investigation at a Michigan laboratory where thousands of dogs are killed every year. After weeks of pressure from the public, the pesticide company that had commissioned a test year-long fungicide test on 32 dogs, agreed that the test was unnecessary and released the dogs to one of our shelter partners so they could be adopted.
• After a recent analysis we performed that showed the 90-day dog test for pesticide registration was rarely used by the Environmental Protection Agency (EPA) to assess the risk that pesticides pose to humans, we are urging the agency to eliminate or significantly limit this test in the near future. We also want the agency to reaffirm their previously stated commitment to end their reliance on using mammals to test pesticides and chemicals by 2035.
• We are asking the Food and Drug Administration (FDA) to support the development of alternative methods that replace dogs in experiments. 
• We want the Department of Veterans Affairs (VA) to adopt the recommendations of an independent panel review released in 2020 that analyzed VA experiments using dogs, identified several areas where dogs are not needed and urged the agency to develop a strategy to replace all animal use. 
• We are recommending that the National Institutes of Health (NIH) scrutinize grant proposals for projects using dogs, by applying strict criteria that must be met before dogs can be used and that they ban the use of dogs in experiments that cause unrelieved pain. We are also requesting that the NIH define a date when they will no longer fund or support experiments on dogs.
• prohibit or limit the use of dogs in experiments not required by federal law, similar to laws passed in California and Illinois .
• ensure an opportunity for  dogs and cats to be adopted into loving homes after the experiment ends.
• strengthen regulatory oversight of facilities that breed dogs destined for laboratories and increase penalties for animal welfare violations.
• Direct state funding to support the research and development of modern non-animal technologies, similar to the law passed in Maryland .

One easy way to help animals suffering in cosmetics tests is to swap out your personal care and household products for cruelty-free versions! Cosmetics (such as shampoo, deodorant and lipstick) and household products (such as dish soap, laundry detergent and glass cleaner) are typically tested on guinea pigs , rabbits ,  mice and rats .

Help us demand better for animals used in experiments through the following actions:

• Tell the FDA to stop encouraging companies to test on animals and instead switch to sophisticated non-animal alternatives.
• Stand with us to end research and tests on dogs by signing our petition.
• Urge the USDA to do their job and help protect animals in laboratories.
• Ask your federal legislators in Congress to ban cosmetic tests on animals.
• Support efforts to replace animal experiments with advanced non-animal alternatives that are better for both human health and animal welfare.

Follow us on Facebook to learn the latest news and actions related to animals in laboratories!

Alternatives to horseshoe crab blood

The Humane Society of the United States urges that horseshoe crab blood be replaced with non-animal methods when conducting endotoxin tests for medical products.

Vaccine, injectable drug and medical device manufacturers must test for endotoxins, a type of bacterial contaminant that, if present, can cause patients to develop symptoms that can include fever, chills, headache and nausea. Blood from horseshoe crabs is used to conduct the Limulus amebocyte lysate (or LAL) test for endotoxins.

The problem

To create this test, horseshoe crabs are captured from the wild and up to 30% of their blood is removed by medical supply companies. The crabs are later returned to the wild; however, it is estimated that 10-15% or more of them die as a result of this process.

In addition to being collected for their blood, horseshoe crabs are gathered up by fisheries, which use them as bait. These practices have led to a rapid decrease in the horseshoe crab population, putting them at risk of extinction. The decrease in wild horseshoe crab populations also impacts other species, including migratory shorebirds like the red knot, a threatened species that depends on horseshoe crab eggs for food.

THE solution

Scientists have developed recombinant Factor C (rFC), a synthetic alternative to the protein in horseshoe crab blood that can detect bacterial endotoxins. Repeated studies have demonstrated that rFC is equivalent or superior to the LAL test. A second method—the monocyte activation test—uses human cells and can not only detect bacterial endotoxins, but also pyrogenic (fever-causing) non-endotoxins.

what should be done

As a member of the Horseshoe Crab Recovery Coalition, the Humane Society of the United States is advocating for the replacement of the Limulus amebocyte lysate test with recombinant Factor C (rFC) or the monocyte activation test (MAT).

We urge the U.S. Pharmacopoeia—which sets quality, purity, strength and identity standards for medicines, food ingredients and dietary supplements—to encourage manufacturers to use rFC or MAT rather than LAL.

We also urge the U.S. Food and Drug Administration to update its guidance for vaccine, injectable drug and device manufacturers to indicate that these non-animal tests are now the preferred methods for endotoxin and pyrogenicity testing.

Donate today and your gift can have TRIPLE the impact to help save more animals from suffering.

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• Published: 01 February 2002

Animal experimentation: the continuing debate

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Nature Reviews Drug Discovery volume  1 ,  pages 149–152 ( 2002 ) Cite this article

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The use of animals in research and development has remained a subject of public debate for over a century. Although there is good evidence from opinion surveys that the public accepts the use of animals in research, they are poorly informed about the way in which it is regulated, and are increasingly concerned about laboratory-animal welfare. This article will review how public concerns about animal experimentation developed, the recent activities of animal-rights groups, and the opportunities and challenges facing the scientific community.

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Is animal research ethical?

Posted: by John Meredith on 16/02/22

More on these Topics:

How can it be right to use an animal for research where we could consider it unethical to use a human being? This is a fundamental question that confronts anybody who benefits from research using animals. If we claim that causing harm to animals is sometimes justifiable where it would be unacceptable to inflict a similar harm or risk on a person, then it seems we are assuming that animals must, in some sense, have less moral value. But is that a justifiable assumption, or is it just a self-serving prejudice? Are there solid rational arguments for treating humans differently from other animals, or are we simply falling back on outmoded habits of thought, a smokescreen that helps us avoid looking the ugly truth of our actions in the eye?

Moral status of animals

In the past, the moral status of animals did not merit a great deal of consideration; raising questions about whether humans were entitled to exploit animals would have struck most people as quaint or absurd. The great moral philosopher Rene Descartes, for example, the man famous for the phrase  cogito ergo sum  - ‘I think therefore I am’ - believed that animals had no inner life at all, that they were essentially as lifeless as clockwork dolls, incapable of emotion, self-awareness, or even feeling pain.  

Such ideas seem laughable to us now. We take it for granted that most animals experience pain and many have complex emotional lives that can depend on relationships with other animals and which can deliver feelings of pleasure and satisfaction. Since Descartes’ day, the growing study of animal behaviour makes this seem obvious, and cleverly designed experiments have confirmed what has been learned from observation, forcing us to acknowledge that sentience – inner life – exists in a great number of other species and sometimes at a very high level. 

But what implications does all this have for the moral consideration of animals? How should it affect the way we treat them? Philosopher Peter Singer, whose book  Animal Liberation  transformed the public debate on animal welfare, believes it should have deep and wide-reaching consequences. Singer argues that it is wrong to inflict harm on a person not because of any cosmic or biblical law about harm but because it is against that person’s interests as they themselves understand them. Considering moral questions in that light, he argues, explodes any idea that we can justify distinctions between individuals based on their sex or race, distinctions that have been passionately defended over many centuries. There are many differences between people of all kinds including, of course, both sexes, but they all have interests that are alike: an interest in avoiding pain or hunger for example. There is no rational basis for preferring the interests of any particular individual, or people of one race or sex class over those of another, that is simply racism and sexism. This is an idea has become widely accepted, if only recently, and it doesn’t seem particularly radical to us today, but Singer takes the idea a step further. 

If there is no non-arbitrary reason to prefer the interests of one human animal over another, how can there be any good reason to prefer the interests of a human animal over a non-human animal? Claims that humans are of special moral interest because of their intelligence or capacity for language or any of the many other things that have been suggested cut no ice.  A less intelligent human has as much interest in avoiding pain as a mathematical genius does, and the same goes for a dog, or a mouse, or a fish. To deny this, says Singer is to make a moral mistake akin to sexism or racism and he calls this way of thinking  speciesism .

One objection to the argument from speciesism is that it implies that there can never be a reason to prefer the welfare of a human being over any other animal where considerations of interest are the same. This strikes most people as counter-intuitive to say the least. Jean Kazez, philosopher and animal rights activist, suggests a thought experiment. Imagine a dedicated vegan responsible for the care of ten young children. It so happens that famine strikes and the children are all in danger of starvation except that our vegan carer owns a cow. Would it be morally acceptable for the vegan to stick by her principles and refuse to slaughter the cow to save the children? If the answer is no, then there seems to be some problem with the speciesist position. It would probably not be considered acceptable to slaughter one of the children to feed the others, after all. So, our intuition is that there must be some foundation for our moral preference for a human over an animal, at least in some extreme conditions. Perhaps the intuition is that there is moral value in feelings of kinship because this is a necessary feeling in order to be a fully healthy human, to flourish as a human being. If that is the case, then, kinship, for humans, is a kind of interest in the Singer sense and one that overrides other interests. That may be why we don’t find it reprehensible when a mother prefers the welfare of her child over that of another.

The moral value of ‘kinship’ overrides speciesism

If kinship carries moral weight, then the speciesist argument loses ground and a possible justification for preferring animals over human beings in research emerges.  Medical research is an attempt to save human lives and reduce human suffering (it has similar benefits for animal as well, of course, but we can set that aside for now, for the sake of simplicity). If, as scientists argue, this can only be achieved with the use of an animal model, then we are morally entitled to prefer the use of a non-human animal, so long as kinship has the moral value we are claiming for it and the suffering and distress of the animals is minimised as much as possible.

But what if this is all just a complicated exercise in justifying what we want to do anyway, what if our moral intuitions are just wrong? It is easy to imagine a Singerian arguing, in the case of our starving children and vegan nanny, that the cow has as much moral standing as any of the others: it has the same interest in living and not suffering the pain of hunger as the others and, what’s more, it may be better able to survive the famine given its ability to eat vegetation that cannot sustain humans. In that case, it seems the advocate of speciesism must argue that they all should starve together in the interests of admirable intellectual rigour, even if it feels a little hard on the children.

Using utility to resolve moral conflicts

As usual, though, the situation is more complicated. Peter Singer and his followers recognise that there is often a conflict of moral interests and so we need a framework for finding a resolution. This framework should not be  ad hoc or arbitrary or based on scripture or any other culturally specific text or tradition but should be rational. Within Singer’s argument the rational moral grounding is provided by utilitarianism the ethical doctrine first proposed by Jeremy Bentham in the 19th century. Utilitarianism argues that when two actions are in conflict, the morally correct one is the one that delivers the most happiness for the largest number (Bentham called this ‘utility’ for obscure reasons). In other words, the morality of an action is decided by its consequences, not by the intentions of the actor or anything else. Applied to the problem of our starving infants and their increasingly paranoid cow, a utilitarian might argue that killing the cow is justified despite it having a similar interest in living to the children because the slaughter would maximise future happiness (utility). If they all die, happiness would be at zero, and if a child was sacrificed to save the others, that would reduce overall happiness because of the distress of the survivors at their loss, the suffering endured by the child selected to die, and the indifference of the cow. 

How do you measure happiness?

Problems with utilitarian ways of thinking immediately suggest themselves: how can happiness be measured? How can the ‘happiness’ of a mouse, for example, be weighed against a person, or any other animal? Must we consider a well-intentioned action that has bad outcomes immoral instead of just unfortunate? The literature goes into all these problems and more at great depth, but for our purposes, it is at least clear that a utilitarian moral framework allows for the use of research animals in some circumstances. The human happiness delivered by a successful medical treatment can be great and long lasting while any pain or distress caused to the experimental animals is kept to a minimum and is of very limited duration. In the utilitarian scales, this tips firmly towards an ethical justification of animal research. It is a surprise to many people that Peter Singer, the father of the modern animal rights movement, comes to the same conclusion, although he argues for stricter controls and more work to reduce and mitigate the use of animals. Even without appealing to concepts such as kinship, in other words, the concept of speciesism, perhaps the most formidable intellectual weapon aimed against animal research by protest groups, does not carry the day. It is perfectly possible to allow the moral value of an animal’s interests and still justify its use in research – even if that research causes the animal harm or distress – so long as the future outcomes maximise happiness. 

Animal rights arguments

The only significant ethical argument against animal research that remains is based on the idea of rights. Just as humans have inalienable rights, the argument goes, so do animals. According to this view, the use of animals for research can never be justified for exactly the same reasons that we cannot justify using humans. But argument from rights has many more problems than argument from interests: from where are rights derived? What specific rights do animals have? Should rights be protected even when this is damaging to the welfare of the animal? This last point is perhaps the most salient. If we allow an animal has a right to its freedom, say, not to be kept in captivity (one of the key rights usually claimed by activists), then we are not only committed to ending all ownership of animals, but to the immediate release of all domestic animals into the wild even if that were to the detriment of the animals’ welfare as it surely would be. The problems mount at every step. How can it be possible to reconcile a vole’s right to life with a falcon’s right to eat? What possible mechanism could be constructed to resolve such conflicts and how much irreparable harm to natural ecosystems would follow if we built one? Without answers to questions like this it is hard to see animal rights arguments as much more than rhetoric.

Maximising future happiness and minimising present suffering is enough for an ethical justification of animal research

The case for ethical animal research, then, does not need as much building as it might at first appear. None of the major philosophical arguments for animal welfare exclude the possibility of ethical animal research. The harm that is done to animals in well-regulated research environments serves a higher moral purpose: the reduction of death and suffering by disease and other disorders. Of course, this is only true if pain, suffering and distress, are minimised – as they are through animal welfare regulations in the UK and EU for example. These regulations also require the application of the principles of the 3Rs – but it is quite obvious, all other things being equal, that the use of a mouse in an investigation into cancer development, for example, will create less suffering than using a person for the same purposes. 

So, a utilitarian calculation of maximising future happiness and minimising present suffering is enough for an ethical justification of animal research even for tough minded opponents of animal exploitation such as Professor Singer. But maybe justification is the wrong word. 

Are we not morally obliged to use animals in research?

If, as the biological sciences are almost unanimous in claiming, we cannot have new medicines without some animal research, and if there are hundreds of devastating human illnesses that will continue to cause misery, pain, and heartache without those new treatments, should we not think of animal research as a moral obligation instead? It is difficult science to do, both technically and emotionally, but if we choose not to carry it out, we are effectively choosing to allow human suffering to continue in the future that our efforts today have the potential to reduce or eliminate. We don’t know which suffering we will be successful in mitigating when, but we can be certain that progress is being made. Remove animal research and we don’t not remove suffering, we simply transfer it from the animals now (where it is carefully controlled and minimised, very often to nothing) to future humans. That is the heart of the ethical case for animal research and one that needs to be better addressed by those who oppose it.

Last edited: 7 April 2022 12:16

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8 Reasons Why Experiments on Animals Must End

Posted by Priya S on January 8, 2019 | Permalink

We could experiment on humans: we’d learn more useful information if we did, and it would be better science. But most of us wouldn’t accept millions of humans being bred to be subjected to dangerous, invasive, and non-consensual tests every year. So why should we allow non-human animals to be deprived of food, water, or sleep or be poisoned, burned, gassed, or electrocuted and then killed?

All sentient beings value life and liberty. That should be reason enough not to subject them to experiments. But here are eight other important reasons why ending experiments on animals would help everyone:

•   Animal-Friendly Methods Are Growing in Number and Popularity From fish and human tissue models to 3-dimensional printing and organs-on-chips, forward-thinking scientists are developing humane, modern, and effective methods. Promising progress has already been made, but significantly more resources must be devoted to the development of animal-free methods.

What You Can Do

Non-animal methods are often faster and more accurate. And where we’ve seen a ban on testing cosmetics on animals, we’ve seen a boom in the development of superior, non-animal tests. All it takes is for the governments to invest more in animal-friendly strategies and for the EU to halt all tests on animals whilst legislators review the law designed to protect animals used in experiments. You can call for them to do just that:

Urge the Government to End All Experiments on Animals

Tell the EU to Halt Tests on Animals

Urge the Dutch Government to End the Use of Non-Human Primates in Animal Experiments

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• About Animal Testing /
• current page Facts and figures on animal testing

Facts and figures on animal testing

Millions of animals are used and killed in scientific procedures every year.

• We estimate that at least 192.1 million animals were used for scientific purposes worldwide in 2015. This is the world’s most reliable figure to date.
• This includes nearly 80 million experiments on animals as well as millions of other animals who are killed for their tissues, used to breed genetically modified animal strains and bred but not used.
• We estimate that the top 10 animal testing countries in the world are China (20.5 million) Japan (15.0 million), the United States (15.6 million), Canada (3.6 million), Australia (3.2 million), South Korea (3.1 million), the United Kingdom (2.6 million), Brazil (2.2 million), Germany (2.0 million) and France (1.9 million), in that order.
• In 2015, an estimated 207,724 tests using dogs and 158,780 tests using monkeys were conducted.
• The top 10 users of dogs were: China, the United States, Canada, South Korea, Japan, Australia, Brazil, the United Kingdom, Germany and India.
• The top 10 users of monkeys were: the United States, China, Japan, Brazil, Canada, the United Kingdom, France, Germany, India and South Korea.
• The latest report from the European Commission shows that 9.3 million experiments were conducted on animals across the EU and Norway in 2022.
• An additional 9.6 million animals were bred and killed, but not used in experiments. This means that in 2022, a total of 18.9 million animals were used for scientific purposes in the EU. 
• The total number of uses decreased by 8% from 2021 to 2022, but the number of tests has risen by 7% since 2020.
• France conducted the highest number of animal uses in Europe in 2022 (2.1 million). Germany was the second highest user completing 1.7 million uses in 2022, while Norway was third with 1.4 million uses that year.
• There were 14,395 uses of dogs in 2022 with France (3,934 uses), Germany (2,873 uses) and Spain (1,511) being the top three users.
• There was a total of 7,658 uses of monkeys across the EU in 2022 with France (4,147 uses), Germany (2,204 uses) and Spain (703 uses) being the top three users.
• Out of the total number of animal uses in the EU in 2022, 33% were for basic research purposes while only 12% were required by regulators.
• Of the 9.3 million uses of animals in 2022, 49% were considered by researchers to have caused moderate or severe suffering to the animals involved.
• Experiments are still being conducted for regulatory purposes in the EU where there are valid non-animal methods available.
• In 2022, there were 3,824 skin irritation tests, 383 eye irritation tests, 33,029 skin sensitisation tests, 19,168 pyrogenicity tests and 152,642 batch potency tests on mice to meet the requirements of human medicines legislation (a large proportion of which were likely to be tests for botox products).  See more.
• According to the latest Government figures, a total of of 2.76 million (2,761,204) procedures on animals were completed in Great Britain in 2022.
• Of these, 1.25 million (45%) related to the creation or breeding of genetically altered animals who were not used in further experiments.
• The remaining 1.51 million (55%) were actual experiments on animals, which included 457,169 experiments (31%) that even the researchers considered had caused moderate or severe suffering to the animals involved.
• There were 20 severe experiments on dogs, up from zero in 2021.
• Out of the total number of procedures conducted in GB in 2022, only 10% were required by law – the rest were conducted voluntarily.
• A total of 4,122 experiments were conducted on dogs in 2022, including 4,014 experiments on beagles and 108 experiments on other breeds.
• A total of 2,197 experiments were conducted on monkeys in 2022, including 72 experiments on marmosets and tamarins, 2,024 experiments on cynomolgus macaques and 101 experiments on rhesus macaques.
• In 2022, 91% of the monkeys used for the first time in experiments were imported from Africa or Asia.
• There was a significant increase in Lethal Dose 50 (LD50) and Lethal Concentration 50 (LC50) tests from 11,758 tests in 2021 to 12,651 in 2022 (up 8%). These cruel and outdated tests are designed to find the dose or concentration of a substance that kills half of the test animals.
• 2022 saw 248 skin sensitisation and 3,198 batch potency tests on mice (a large proportion of which were likely to be tests for botox products). While these are significant decreases compared to the previous year – particularly for batch potency testing – these are areas in which animals should not be used at all due to the availability of validated replacements. See more .
• We celebrate that, for the first time, zero skin irritation tests on animals were conducted in GB in 2022. Last year we celebrated that, for the first time, zero eye irritation tests on animals were conducted on animals in 2021. Sadly, 2022 saw three eye irritation tests on rabbits, demonstrating that this use has not ended completely.

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Find out more about animal testing.

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Alternatives to animal testing

subtitle: Alternatives to animal tests are often cheaper, quicker and more effective.

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subtitle: Established in 1898, Cruelty Free International is firmly rooted in the early social justice movement and has a long and inspiring history.

Animals used in laboratories are deliberately harmed, not for their own good, and are usually killed at the end of the experiment.

What is animal testing?

subtitle: Animals used in laboratories are deliberately harmed, not for their own good, and are usually killed at the end of the experiment.

Animal experiments are cruel, unreliable, and even dangerous.

Arguments against animal testing

subtitle: Animal experiments are cruel, unreliable, and even dangerous.

Animal testing is carried out in a wide range of areas, including biological research, and testing medicines and chemicals.

Types of animal testing

subtitle: Animal testing is carried out in a wide range of areas, including biological research, and testing medicines and chemicals.

Science Publications

Why Do Scientists Experiment on Animals?

Animal studies in science are experiments that control an animal's behaviour or physiology for study, often to serve as a model for human biology where testing on humans is impractical or unethical.

The species or classification of animals used in testing largely depends on the goal of the experiment.

For example, zebrafish are quick to breed, easy to house, and transparent as embryos - but they also carry 70 percent of the genes found in humans. All this makes them suitable for studies on human disease and embryological development.

Rodents have a long history of being used for science experiments, and today make up around three quarters of all animal subjects in testing. Easy to raise and breed, their mammalian physiology and genomes overlap even more considerably with those of humans, making them suitable models for studying behaviours, toxicology, and the effects of medical treatments.

Non-human primates , especially chimpanzees and rhesus monkeys, have also been used extensively in scientific testing. While harder to reproduce in large numbers and challenging to house comfortably, experiments on our closest evolutionary relatives can yield valuable information on a wide range of issues, from drug toxicity to neurology.

However, the close likeness of non-human primates to ourselves also means their use in experiments is the most controversial of all types of animal testing. Generally, data across different countries, including the European Union , show that non-human primate research constitutes less than 1 percent of all animal studies.

However, studies on monkeys aren't yet phased out: In 2017, the US had a record-high number of studies involving monkeys.

How useful are animal models in experiments?

If conducted under strict methods with appropriate protocols, animal experimentation can provide reliable evidence on how that animal's physiology or behaviour responds under the experiment's conditions; genetic studies are particularly effective, while behavioural studies can yield less firm conclusions.

Unfortunately, the nature of experiments that make use of animal models can often lend themselves to being poorly designed, conducted, or analysed. There can also be a sex imbalance, with much of rodent research done only on male mice , for example.

Experiments that apply the findings to human biology require significant assumptions on whether any differences between them are significant. Even where animals are genetically altered to better reflect human biochemistry, there is always the risk that an unidentified behaviour or function might mean the experimental results can't be applied to humans.

This doesn't make animal models useless. As with all experiments, the weight of replicated experiments performed critically under peer review determines how confident we should be in a set of results.

It does mean we ought to be cautious about how results from an experiment based on an animal model might apply to our own bodies.

What are the ethics of testing on animals?

Concerns surrounding experiments using animal models are often based on the morality of depriving animals of their liberty or subjecting them to pain or discomfort, to meet a human need or value.

At an extreme end of the ethics spectrum is the claim that all animals have rights equal to humans, and therefore any experiment that wouldn't ethically be conducted on humans shouldn't be conducted on any animal.

Ethics boards today tend to weigh up the potential benefits of an experiment with the risks of harm and suffering to the animal. However, what constitutes a benefit , as well as objective ways to define acceptable limits of harm, pain, and discomfort in different animals can make this more challenging than first appears.

What is the future of animal testing?

More than half a century ago, zoologists William Russell and Rex Burch suggested experimentation should become more humane by following the three Rs; restrict when to use animals; refine the kinds of experiments conducted on them; and replace as the technology becomes available.

Advances in computer modelling and in-vitro tissue culture design are continuing to provide alternatives to animal models that don't suffer from the same ethical and practical limitations.

Human tissue models, such as those making up 3D tissue conglomerates called organoids , are increasingly serving as appropriate models for studying growth and development.

These solutions might not make the way we conduct the experiments themselves more trustworthy. But with robust debate and reliable review procedures, they will steadily make animal testing - and the ethical and practical problems they bring - a thing of the past.

All Explainers are determined by fact checkers to be correct and relevant at the time of publishing. Text and images may be altered, removed, or added to as an editorial decision to keep information current.

Ethical care for research animals

WHY ANIMAL RESEARCH?

The use of animals in some forms of biomedical research remains essential to the discovery of the causes, diagnoses, and treatment of disease and suffering in humans and in animals., stanford shares the public's concern for laboratory research animals..

Many people have questions about animal testing ethics and the animal testing debate. We take our responsibility for the ethical treatment of animals in medical research very seriously. At Stanford, we emphasize that the humane care of laboratory animals is essential, both ethically and scientifically.  Poor animal care is not good science. If animals are not well-treated, the science and knowledge they produce is not trustworthy and cannot be replicated, an important hallmark of the scientific method .

There are several reasons why the use of animals is critical for biomedical research: 

••  Animals are biologically very similar to humans. In fact, mice share more than 98% DNA with us!

••  Animals are susceptible to many of the same health problems as humans – cancer, diabetes, heart disease, etc.

••  With a shorter life cycle than humans, animal models can be studied throughout their whole life span and across several generations, a critical element in understanding how a disease processes and how it interacts with a whole, living biological system.

The ethics of animal experimentation

Nothing so far has been discovered that can be a substitute for the complex functions of a living, breathing, whole-organ system with pulmonary and circulatory structures like those in humans. Until such a discovery, animals must continue to play a critical role in helping researchers test potential new drugs and medical treatments for effectiveness and safety, and in identifying any undesired or dangerous side effects, such as infertility, birth defects, liver damage, toxicity, or cancer-causing potential.

U.S. federal laws require that non-human animal research occur to show the safety and efficacy of new treatments before any human research will be allowed to be conducted.  Not only do we humans benefit from this research and testing, but hundreds of drugs and treatments developed for human use are now routinely used in veterinary clinics as well, helping animals live longer, healthier lives.

It is important to stress that 95% of all animals necessary for biomedical research in the United States are rodents – rats and mice especially bred for laboratory use – and that animals are only one part of the larger process of biomedical research.

Our researchers are strong supporters of animal welfare and view their work with animals in biomedical research as a privilege.

Stanford researchers are obligated to ensure the well-being of all animals in their care..

Stanford researchers are obligated to ensure the well-being of animals in their care, in strict adherence to the highest standards, and in accordance with federal and state laws, regulatory guidelines, and humane principles. They are also obligated to continuously update their animal-care practices based on the newest information and findings in the fields of laboratory animal care and husbandry.  

Researchers requesting use of animal models at Stanford must have their research proposals reviewed by a federally mandated committee that includes two independent community members.  It is only with this committee’s approval that research can begin. We at Stanford are dedicated to refining, reducing, and replacing animals in research whenever possible, and to using alternative methods (cell and tissue cultures, computer simulations, etc.) instead of or before animal studies are ever conducted.

Organizations and Resources

There are many outreach and advocacy organizations in the field of biomedical research.

• Learn more about outreach and advocacy organizations

Stanford Discoveries

What are the benefits of using animals in research? Stanford researchers have made many important human and animal life-saving discoveries through their work. 

• Learn more about research discoveries at Stanford

Animal experimentation

Nonhuman animals are used in laboratories for a number of purposes. Examples of animal experimentation include product testing, use of animals as research models and as educational tools. Within each of these categories, there are also many different purposes for which they are used. For instance, some are used as tools for military or biomedical research; some to test cosmetics and household cleaning products, and some are used in class dissection to teach teenagers the anatomy of frogs or to have a subject for a Ph.D. dissertation.

The number of animals used in animal experimentation is certainly smaller than that of those used in others such as animal farming or the fishing industry. 1  Yet it has been estimated to be well above 100 million animals who are used every year. 2

The ways in which these animals can be harmed in experimental procedures, also known as vivisection, 3 vary. In almost all cases they are very significant and the majority of them end with the death of the animals.

There’s an important difference today between the consideration that is afforded to the potential and actual subjects used in experiments, depending on whether they are human or nonhuman animals. Few people today would condone experimenting on human beings in harmful ways, and in fact, indicative of this, such research is strongly restricted by law, when it isn’t just prohibited outright. When experimentation on humans is permitted it is always in a context of the individuals involved consenting to it, for whatever personal benefit that serves as an incentive for them. For nonhuman animals, this is not the case.

This is not because of any belief that experimentation on humans could not bring about important knowledge (in fact, it seems obvious that this practice would uncover far more useful and relevant knowledge than any experimentation on nonhuman animals ever can). Rather, the reason for this double standard is that nonhuman animals are not morally taken into account because the strong arguments against speciesism are not considered.

In the following sections the most important areas in which nonhuman animals are used in laboratories or classrooms, as well as the research methods that don’t use them, are addressed.

Animals used for experimentation

Environmental research.

Animals are made to suffer and are killed to test the impact that chemicals can have in the environment. Some of the most important environmentalist organizations have been lobbying for this practice and have often been successful despite the opposition of animal defenders.

Cosmetic and household products testing

While animal testing of new cosmetics and household products is now illegal in places such as the European Union and India, it’s still being carried out in the U.S. and other places, where many animals are blinded, caused extreme pain and killed.

Military experimentation

The use of animals to test new weaponry, bullets and warfare chemicals, as well as the effects of burns and poison for military purposes, remains mainly hidden today, but many animals die in terrible ways because of it.

Biomedical experimentation

Animals of a variety of species are harmed for numerous purposes in biomedical research because the non-animal methodologies aren’t implemented. Those animals are harmed in many ways that most people ignore.

Experimentation with new materials

When new materials are developed, they are often tested by using methods such as cell or tissue cultures, or computational models. However, materials are also commonly tested on animals who are killed afterwards.

Animals used in education

Animals used in primary and secondary education.

Dissecting animals and using them in other ways has been common practice in the U.S. and some other countries in primary and especially secondary education for many years. This means killing a huge number of animals and educating new generations in the idea that it’s acceptable to harm animals for our benefit.

Animals used in higher education

In the science departments of many different universities, research, teaching and training are successfully carried out without using animals as laboratory tools. However, animals are still subjected to all kind of procedures in many other places.

Towards a future without animals harmed in laboratories

Research methods that do not involve the use of nonhuman animals.

Defenders of animal experimentation often claim that there is no choice but to harm animals lest scientific progress be stopped, but this is not so. There are many non-harmful methods available today.

Companies that test on animals

Despite the fact that many other companies do not experiment on sentient animals, there are still companies that choose to continue carrying out animal tests out of a lack of will to implement new methods.

Companies that do not test on animals

Fortunately, although many companies today choose not to harm animals in product development, quality and safety isn’t affected in the least.

1 Every year tens of billions are killed in slaughterhouses and trillions are fished and killed in fish factories. For estimations regarding this see: Food and Agriculture Organization of the United Nations (2021) “ Livestock primary ”, FAO STAT , February 19 [accessed on 24 March 2013]. See also Mood, A. &  Brooke, P. (2010) “ Estimating the number of fish caught in global fishing each year ”, Fishcount.org.uk , July [accessed on 18 October 2020]; (2012) “ Estimating the number of farmed fish killed in global aquaculture each year ”, Fishcount.org.uk , July [accessed on 18 January 2021].

2  See Taylor, K.; Gordon, N.; Langley, G. & Higgins, W. (2008) “Estimates for worldwide laboratory animal use in 2005”,  Alternatives to Laboratory Animals , 36, pp. 327-342.

3 Although the term “vivisection” literally means “cutting a living animal,” this word has broadened its meaning in common language to denote any kind of laboratory invasive use of an animal. Defenders of animal experimentation prefer not to use it due to its negative connotations. Opponents of it claim that there shouldn’t be a problem with using this term given the meaning it already has in common language. They argue that its rejection is due to an intention to use language that is not explicit about how animals are used in this field.

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Why We Still Test on Animals, Explained

A fraught regulatory environment and human stubbornness help explain the roadblocks.

Explainer • Research • Science

Words by Marlena Williams

In a bustling laboratory at the Harvard Stem Cell Institute, hundreds of scientists are busy creating self-organizing, three-dimensional tissue cultures known as organoids out of stem cells. These tiny cell cultures, ranging in size from the width of a hair to five millimeters, are capable of replicating the complexity of real human organs. In practical terms, scientists can — and already are — replicating human kidneys, brains, lungs, intestines, stomachs and livers. The technology offers us a huge opportunity to shift the way we test drugs, foods and cosmetic products. Scaled up, organoids could also eliminate the need to use animals in research and testing . By replicating the complexity and specificity of human organs, organoids offer an accurate, cost-effective and humane alternative to using animal models, so why aren’t we using them?

Organoids aren’t the only promising alternative on the horizon. From organs-on-chips — 3D devices that look and function like human organs — to highly sophisticated computer modeling systems , there are more alternatives to animal testing today than ever before.

And yet laboratory animals remain the dominant means by which we test products, with more than 115 million animals tested annually , to develop new drugs and study both human and animal diseases. While animal testing has certainly helped to usher in many life-saving medical and scientific advancements over the years — including the discovery of penicillin and the development of the polio vaccine — it comes with its own unique set of limitations and concerns.

Animals respond differently to drugs and stimuli than humans, especially when confined in the highly artificial and stressful environment of a lab, and testing on animals often creates unreliable and hard-to-replicate results. About 90 percent of drugs fail once they reach the human clinical trial stage. There are a variety of reasons why this happens, researchers say, including the fact that medicines function differently in the cells of one of the most common lab animals, mice , as compared to humans.

Animal testing is also expensive. The estimated dollar costs to bring a drug to market could be as much as $1 billion, give or take, to more than $2 billion in total, and for cancer drugs, can take more than a decade to hit the market .

So why are we still using laboratory animals, especially when so many other promising alternatives exist? This remains an incredibly fraught and complicated question, one that has divided scientists, animal advocates and even most Americans , for centuries.

Animal Testing: An Overview

There is no one definitive type of animal testing . Animals are tested on in a wide variety of ways, in a wide variety of settings, for a wide variety of reasons.

Scientific and medical researchers use animals to develop new drugs and vaccines, study biological systems and to advance new surgical procedures and treatment methods. Many commercial industries use laboratory animals to test the safety of their cosmetics, household cleaners, food additives, pesticides, chemicals and other potentially harmful substances, either by conducting the tests themselves or by contracting with third party companies.

Laboratory animals are also used in the classroom , in the military and even in outer space .

While there is no definitive number of how many animals are used in total in research and testing, it is estimated that more than 50 million laboratory animals are used in the United States each year. Rats and mice make up 85-95% of animal research subjects here, but dogs, monkeys, rabbits, guinea pigs, fish and birds are also widely used across many industries.

Until the 1960s, there were no federal laws regulating animal research or setting standards for laboratory animal welfare. With no federal oversight, the animal testing world was a sort of wild west , where researchers obtained their animal subjects from questionable sources — like unlicensed dealers and overcrowded animal shelters — and held them in often deplorable facilities, conducting a variety of cruel and unnecessary experiments and procedures on them without anesthesia or other pain management interventions.

The Animal Welfare Act was passed in 1966, largely in response to a disturbing story of a Dalmatian named Pepper who was stolen from her family home in Pennsylvania by an unscrupulous dealer and sold to a hospital in New York, where she was experimented on, killed and then incinerated. Pepper’s story — along with a sensational Life magazine article on dog dealers titled “ Concentration Camps for Dogs ” — spurred the welfare act’s passage and ushered in long overdue welfare protections for laboratory animals, including minimum standards for humane care, a registration system for testing facilities and a clear ban on the use of stolen animals in experiments.

A strategy known as the 3 R’s —  short for Replacement, Reduction, and Refinement — quickly became the guiding principles for humane animal experimentation in the twentieth century, and remain so to this day. The idea is to reduce the number of animals used in testing and improve animal welfare conditions as much as possible.

The Animal Welfare Act — amended in 1985 to make research facilities more accountable — and the Health Research Extension Act that followed were designed to minimize the pain and stress experienced by laboratory animals, not to completely eliminate their use or explore non-animal alternatives.

Legal scholar and animal ethicist Paul Locke argues that the “keys to the laboratory” remain firmly in the hands of researchers . These scientists have little oversight and only have to report the most egregious failures and abuses to federal authorities. What’s more, any researchers who want to treat animals more humanely are often hamstrung by institutional practice, career pressures and a general culture that views animal testing as a “necessary evil.”

Proponents of animal testing often argue that animal models are justified because the benefits to humans outweigh concerns about animal suffering. But as more testing alternatives emerge, the reasons for sticking with animals begin to dwindle. At this point, there are countless technological advancements that could make both human and animal subjects unnecessary.

But despite the promise of these non-animal models, many institutions and researchers cling to the status quo —in part out of a resistance to change, but also a lack of real investment in proven alternatives and political tensions within competing movements.

“The American Chamber of Horrors”

In 1933, one woman died and more than a dozen others were blinded after using a permanent mascara and eyebrow dye called Lash Lure , which contained an untested chemical derived from coal tar called p-phenylenediamine. Lash Lure caused painful blisters, abscesses and ulcers in and around the eyes of its unsuspecting consumers, some of whom were photographed and featured in a display at the 1933 Chicago World Fair that one journalist referred to as “ The American Chamber of Horrors .”

Just a few years later, 107 people, mostly children, died after ingesting the anti-bacterial drug Elixir Sulfanilamide , which contained a sweet-tasting ingredient also found in antifreeze.

The public outcry following the Lash Lure and Elixir Sulfanilamide tragedies prompted Congress to pass the Food, Drug and Cosmetic Act in 1938, the first law in the country to regulate the steadily growing pharmaceutical and cosmetics industries. The FDCA required cosmetics manufacturers to submit evidence of a product’s safety and effectiveness before marketing it to the general public. Animal testing quickly became the default way for cosmetics companies to ensure the safety of their products and to potentially avoid criminal liability for placing a harmful product on the market. Though the original FDCA didn’t require animal testing for cosmetics like it did for drugs, the agency still highly encouraged companies to test their products on animals.

One of the most common cosmetics testing methods involved “acute ocular toxicity,” or Draize, tests , named after the FDA scientist who invented the method in the 1940s. These tests involved restraining a conscious, unanesthetized rabbit and applying the chemical or product directly to its eyes. The substance was left on the eyeball for a set period of time, and the animal was then monitored for up to 14 days for signs of redness, swelling, hemorrhaging or irritation.

Draize tests remained the gold standard for FDCA compliance until a highly visible campaign, led by activist Henry Spira, drew attention to the tests in the 1980s. Spira ran an ad in the New York Times showing a blind laboratory bunny beneath the headline, “How many rabbits does Revlon blind for beauty’s sake?” The ad and resulting campaign brought increased attention to the cruelty of animal testing and prompted many brands to start searching for alternatives.

But cosmetics testing remains common , even in the 21st century. When companies choose to develop or use new ingredients in their products, they may still decide to conduct tests on animals to assess the safety of the product. No one wants to be responsible for another Lash Lure tragedy. Such tests, however, are now completely unnecessary: the FDCA does not explicitly require animal testing for cosmetics — only clearly demonstrated safety — and there are already thousands of ingredients available that have proven histories of safe and effective use.

By far the biggest factor keeping companies from going fully cruelty-free is China, which long required all cosmetics that entered its borders to be tested on animals. Though China has recently amended its regulations to exempt some imported products from mandatory testing, the country still requires animal testing for many popular cosmetics. Beauty companies that want to sell into the massive Chinese market–which accounted for a whopping $88 billion dollar sales in 2021 alone—must allow their products to be tested on animals.

While many cosmetics companies have decided to maintain their cruelty-free status and not sell or market their products in China, some of the biggest beauty companies like Revlon and L’Oreal, which in turn own dozens of other smaller beauty companies, do sell there. Though these companies will often adamantly deny using animal testing, they often do allow animal testing when required by law , likely meaning in China.

But the law elsewhere in the world is rapidly changing. The European Union banned cosmetics testing in 2013 , and dozens of other countries, including Mexico, Canada, Australia and India, quickly followed suit. Though there is currently no federal law in the United States banning cosmetics testing outright, twelve U.S states prohibit the sale of products tested on animals within their borders.

Unlikely Allies and Foes

Voters and consumers are understandably horrified by the idea of rubbing hairspray or perfume into the eyes of helpless white rabbits just so we can defrizz our hair or smell a little better. But making political and social progress on other forms of animal testing is a far more difficult task. When it comes to toxicity testing , progress towards alternative methods has long been delayed by an often surprising web of conflicts between environmentalists, animal advocates, government agencies and polluting corporations.

Take, for example, the case of the Environmental Protection Agency. In September 2019, Andrew Wheeler, the head of the EPA under Donald Trump, announced that the agency would reduce animal toxicity tests by 30 percent by 2025 and stop these experiments altogether by 2035.

Under the Toxic Substances Control Act , the EPA is empowered to conduct and oversee a massive amount of animal testing — involving anywhere from 20,000 to 100,000 animals annually —in order to determine the effects of certain chemicals or pollutants on fertility, development, genetics and overall health. These tests often involve pumping chemicals straight into an animal’s stomach or forcing animals to inhale potentially lethal chemicals in a gas chamber.

The Food, Drug and Cosmetics Act further authorizes the EPA to regulate pesticides . When registering a new pesticide, the EPA requires companies to perform a 90-day oral toxicity study on both rodent and non-rodent species — typically cats and dogs —as part of its human health risk assessment. A 2019 undercover investigation by the Humane Society of the United States revealed dozens of beagles being force-fed varying doses of pesticides at a Dow AgroSciences facility in order to test their toxicity as required by the EPA.

But Wheeler’s decision to roll back animal testing requirements was immediately criticized by people within the environmental movement, who accused the administrator of bowing to pressure from the powerful chemical industry . Chemical giants like Dow and DuPont tend to balk at such testing because it is both time-consuming and expensive.

While Wheeler maintained that his decision was based out of his love for animals, it wasn’t a logical jump to assume that the Trump administration was favoring polluting industries over the health of American citizens and the environment. Major environmental groups like the National Resources Defense Counsel have since come out in support of animal toxicity tests .

These debates show the political thorniness of the toxicity testing debate, which pits environmental groups against the agency tasked with protecting the environment, and aligns animal advocates with the conservatives and big businesses they often oppose.

While animal toxicity tests may prevent potentially dangerous chemicals from harming people, other animals and the environment, these tests are less fool-proof than the agency’s reliance on them might suggest. One study found oral toxicity testing on dogs to be an unnecessary step , and another showed that rodent models accurately predicted human toxicity in only 43 percent of cases. Lethal dose tests, whereby animals are forced to swallow large amounts of chemicals to determine the amount that causes death, are considered impractical, as most humans are exposed to these harmful substances at far slower rates and in far smaller doses.

The National Academy of the Sciences has been urging a shift away from animal testing since 2007. Thanks to a grant from the EPA, scientists at Johns Hopkins have been working to develop lab grown “mini-brains” that may enable researchers to study neurotoxic effects without the need for animal subjects. Even simple changes, like improving the searchability of the EPA’s current testing data , could dramatically reduce the need to test chemicals and pesticides on animals.

But in another twist, it now seems that under the Biden administration, the EPA has scrapped its plans to eliminate animal testing , instead opting for the vague goal of reducing reliance on animal models and researching viable alternatives.

New non-animal models will require rigorous regulatory approval before they are accepted, and even proponents of these alternatives think they are still a long way off from becoming the norm. A potent mix of government inertia, political volatility and public skepticism towards new methods may favor the status quo over more humane and effective alternatives.

Cures vs. Creatures

The toxicity debates look tame compared to the contentious, often ugly debates that have been raging between animal advocates and the medical and scientific community since at least the 19th century.

Professor Paul Locke calls this the “cures vs. creatures” dilemma. On the one hand, there is deep societal respect and need for the doctors and scientists who rely on animal models to better understand human biology, cure horrible diseases and prevent future harms.

But on the other hand, there is an equally strong societal force that believes animals are sentient creatures deserving of protections and rights. Animal advocates find something deeply hypocritical about a research model that uses animal subjects because of their similarity to humans while refusing to acknowledge that these creatures are capable of many of the same emotions and sensations as us.

“To avoid seeing this double treatment as a problem, and thus to avoid ethical reflection on it, requires an extraordinary level of self-deception, rationalization, and selective blindness,” writes scientist John Gluck in his book, Voracious Science and Vulnerable Animals . “It requires [researchers] to objectify experimental animals, categorically excluding them from the class of beings requiring full ethical considerations.”

Both sides of the “cures vs. creatures” dilemma deploy rousing narratives and imagery to prove the nobility of their cause. Animal activists can shock and horrify with nightmarish stories about the thousands of dogs , cats , monkeys and rodents who suffer in labs, while doctors and researchers can comfort and inspire with stories of the life-saving medical advancements that have benefited from animal testing, from the cure for smallpox to the COVID-19 vaccine . But these competing narratives can help to keep the animal testing debate polarized and forestall any effective progress towards widely available non-animal alternatives that could both eliminate animal suffering and offer more accurate, reliable and cost-effective results.

Scholars and animal advocates like Paul Locke believe that animal models will be needed as medical and scientific tools until enough money is pumped into the system to support and vet non-animal alternatives. While technologies like organoids, organs-on-chips and computer simulations show great promise for future advancements, there has not been enough institutional interest or investment in these alternatives to make a meaningful difference in transforming the current system.

In 2023, President Biden signed into law an amendment to the FDCA removing the requirement that pharmaceutical companies test their drugs on animals before moving on to human clinical trials. Testing is no longer required, but it may still be encouraged by the agency if they believe it is useful or necessary. Last year’s federal budget also included $5 million dollars for a new FDA program designed to develop and encourage non-animal testing methods.

But $5 million dollars is a mere drop in the bucket of the FDA’s massive $8.4 billion federal budget and is hardly enough to support the large-scale institutional shift that will be necessary to replace animal testing with non-animal alternatives. If the National Institute of Health invested just 1 percent of its whopping $48 billion dollar budget in exploring non-animal alternatives, for example, we could make significant progress towards shifting away from animal testing, at least when it comes to scientific and medical research.

The Bottom Line

Laboratory animals receive certain minimal welfare protections under the law, but they continue to be used by the millions for research testing for a wide range of industries — from food to fashion to biomedical research — despite the alternatives.

For researchers to shift to using these new methods, we may just need to, as scientist John Gluck writes , “rethink and re-form the entire framework of beliefs that underlies our relationship with nonhuman species.” But that kind of rethinking will require a serious national conversation about the place of animals in society, and how they should be treated and perceived, in the laboratory and beyond.

Independent Journalism Needs You

Marlena Williams is a writer from Portland, Oregon. She is the author of the essay collection Night Mother: A Personal and Cultural History of the Exorcist.

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• v.63(2 Suppl 3); 2022 Jun

Ethical considerations regarding animal experimentation

Aysha karim kiani.

1 Allama Iqbal Open University, Islamabad, Pakistan

2 MAGI EUREGIO, Bolzano, Italy

DEREK PHEBY

3 Society and Health, Buckinghamshire New University, High Wycombe, UK

GARY HENEHAN

4 School of Food Science and Environmental Health, Technological University of Dublin, Dublin, Ireland

RICHARD BROWN

5 Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada

PAUL SIEVING

6 Department of Ophthalmology, Center for Ocular Regenerative Therapy, School of Medicine, University of California at Davis, Sacramento, CA, USA

PETER SYKORA

7 Department of Philosophy and Applied Philosophy, University of St. Cyril and Methodius, Trnava, Slovakia

ROBERT MARKS

8 Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel

BENEDETTO FALSINI

9 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy

NATALE CAPODICASA

10 MAGI BALKANS, Tirana, Albania

STANISLAV MIERTUS

11 Department of Biotechnology, University of SS. Cyril and Methodius, Trnava, Slovakia

12 International Centre for Applied Research and Sustainable Technology, Bratislava, Slovakia

LORENZO LORUSSO

13 UOC Neurology and Stroke Unit, ASST Lecco, Merate, Italy

DANIELE DONDOSSOLA

14 Center for Preclincal Research and General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca‘ Granda Ospedale Maggiore Policlinico, Milan, Italy

15 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

GIANLUCA MARTINO TARTAGLIA

16 Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy

17 UOC Maxillo-Facial Surgery and Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milan, Italy

MAHMUT CERKEZ ERGOREN

18 Department of Medical Genetics, Faculty of Medicine, Near East University, Nicosia, Cyprus

MUNIS DUNDAR

19 Department of Medical Genetics, Erciyes University Medical Faculty, Kayseri, Turkey

SANDRO MICHELINI

20 Vascular Diagnostics and Rehabilitation Service, Marino Hospital, ASL Roma 6, Marino, Italy

DANIELE MALACARNE

21 MAGI’S LAB, Rovereto (TN), Italy

GABRIELE BONETTI

Astrit dautaj, kevin donato, maria chiara medori, tommaso beccari.

22 Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy

MICHELE SAMAJA

23 MAGI GROUP, San Felice del Benaco (BS), Italy

STEPHEN THADDEUS CONNELLY

24 San Francisco Veterans Affairs Health Care System, University of California, San Francisco, CA, USA

DONALD MARTIN

25 Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, SyNaBi, Grenoble, France

ASSUNTA MORRESI

26 Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy

ARIOLA BACU

27 Department of Biotechnology, University of Tirana, Tirana, Albania

KAREN L. HERBST

28 Total Lipedema Care, Beverly Hills California and Tucson Arizona, USA

MYKHAYLO KAPUSTIN

29 Federation of the Jewish Communities of Slovakia

LIBORIO STUPPIA

30 Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, University "G. d'Annunzio", Chieti, Italy

LUDOVICA LUMER

31 Department of Anatomy and Developmental Biology, University College London, London, UK

GIAMPIETRO FARRONATO

Matteo bertelli.

32 MAGISNAT, Peachtree Corners (GA), USA

Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred birds comprise almost 90% of the animals that are used for research purpose. However, growing awareness of the sentience of animals and their experience of pain and suffering has led to strong opposition to animal research among many scientists and the general public. In addition, the usefulness of extrapolating animal data to humans has been questioned. This has led to Ethical Committees’ adoption of the ‘four Rs’ principles (Reduction, Refinement, Replacement and Responsibility) as a guide when making decisions regarding animal experimentation. Some of the essential considerations for humane animal experimentation are presented in this review along with the requirement for investigator training. Due to the ethical issues surrounding the use of animals in experimentation, their use is declining in those research areas where alternative in vitro or in silico methods are available. However, so far it has not been possible to dispense with experimental animals completely and further research is needed to provide a road map to robust alternatives before their use can be fully discontinued.

How to cite this article: Kiani AK, Pheby D, Henehan G, Brown R, Sieving P, Sykora P, Marks R, Falsini B, Capodicasa N, Miertus S, Lorusso L, Dondossola D, Tartaglia GM, Ergoren MC, Dundar M, Michelini S, Malacarne D, Bonetti G, Dautaj A, Donato K, Medori MC, Beccari T, Samaja M, Connelly ST, Martin D, Morresi A, Bacu A, Herbst KL, Kapustin M, Stuppia L, Lumer L, Farronato G, Bertelli M. Ethical considerations regarding animal experimentation. J Prev Med Hyg 2022;63(suppl.3):E255-E266. https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2768

Introduction

Animal model-based research has been performed for a very long time. Ever since the 5 th century B.C., reports of experiments involving animals have been documented, but an increase in the frequency of their utilization has been observed since the 19 th century [ 1 ]. Most institutions for medical research around the world use non-human animals as experimental subjects [ 2 ]. Such animals might be used for research experimentations to gain a better understanding of human diseases or for exploring potential treatment options [ 2 ]. Even those animals that are evolutionarily quite distant from humans, such as Drosophila melanogaster , Zebrafish ( Danio rerio ) and Caenorhabditis elegans , share physiological and genetic similarities with human beings [ 2 ]; therefore animal experimentation can be of great help for the advancement of medical science [ 2 ].

For animal experimentation, the major assumption is that the animal research will be of benefit to humans. There are many reasons that highlight the significance of animal use in biomedical research. One of the major reasons is that animals and humans share the same biological processes. In addition, vertebrates have many anatomical similarities (all vertebrates have lungs, a heart, kidneys, liver and other organs) [ 3 ]. Therefore, these similarities make certain animals more suitable for experiments and for providing basic training to young researchers and students in different fields of biological and biomedical sciences [ 3 ]. Certain animals are susceptible to various health problems that are similar to human diseases such as diabetes, cancer and heart disease [ 4 ]. Furthermore, there are genetically modified animals that are used to obtain pathological phenotypes [ 5 ]. A significant benefit of animal experimentation is that test species can be chosen that have a much shorter life cycle than humans. Therefore, animal models can be studied throughout their life span and for several successive generations, an essential element for the understanding of disease progression along with its interaction with the whole organism throughout its lifetime [ 6 ].

Animal models often play a critical role in helping researchers who are exploring the efficacy and safety of potential medical treatments and drugs. They help to identify any dangerous or undesired side effects, such as birth defects, infertility, toxicity, liver damage or any potential carcinogenic effects [ 7 ]. Currently, U.S. Federal law, for example, requires that non-human animal research is used to demonstrate the efficacy and safety of any new treatment options before proceeding to trials on humans [ 8 ]. Of course, it is not only humans benefit from this research and testing, since many of the drugs and treatments that are developed for humans are routinely used in veterinary clinics, which help animals live longer and healthier lives [ 4 ].

COVID-19 AND THE NEED FOR ANIMAL MODELS

When COVID-19 struck, there was a desperate need for research on the disease, its effects on the brain and body and on the development of new treatments for patients with the disease. Early in the disease it was noticed that those with the disease suffered a loss of smell and taste, as well as neurological and psychiatric symptoms, some of which lasted long after the patients had “survived” the disease [ 9-15 ]. As soon as the pandemic started, there was a search for appropriate animal models in which to study this unknown disease [ 16 , 17 ]. While genetically modified mice and rats are the basic animal models for neurological and immunological research [ 18 , 19 ] the need to understand COVID-19 led to a range of animal models; from fruit flies [ 20 ] and Zebrafish [ 21 ] to large mammals [ 22 , 23 ] and primates [ 24 , 25 ]. And it was just not one animal model that was needed, but many, because different aspects of the disease are best studied in different animal models [ 16 , 25 , 26 ]. There is also a need to study the transmission pathways of the zoonosis: where does it come from, what are the animal hosts and how is it transferred to humans [ 27 ]?

There has been a need for animal models for understanding the pathophysiology of COVID-19 [ 28 ], for studying the mechanisms of transmission of the disease [ 16 ], for studying its neurobiology [ 29 , 30 ] and for developing new vaccines [ 31 ]. The sudden onset of the COVID-19 pandemic has highlighted the fact that animal research is necessary, and that the curtailment of such research has serious consequences for the health of both humans and animals, both wild and domestic [ 32 ] As highlighted by Adhikary et al. [ 22 ] and Genzel et al. [ 33 ] the coronavirus has made clear the necessity for animal research and the danger in surviving future such pandemics if animal research is not fully supported. Genzel et al. [ 33 ], in particular, take issue with the proposal for a European ban on animal testing. Finally, there is a danger in bypassing animal research in developing new vaccines for diseases such as COVID-19 [ 34 ]. The purpose of this paper is to show that, while animal research is necessary for the health of both humans and animals, there is a need to carry out such experimentation in a controlled and humane manner. The use of alternatives to animal research such as cultured human cells and computer modeling may be a useful adjunct to animal studies but will require that such methods are more readily accessible to researchers and are not a replacement for animal experimentation.

Pros and cons of animal experimentation

Arguments against animal experimentation.

A fundamental question surrounding this debate is to ask whether it is appropriate to use animals for medical research. Is our acceptance that animals have a morally lower value or standard of life just a case of speciesism [ 35 ]? Nowadays, most people agree that animals have a moral status and that needlessly hurting or abusing pets or other animals is unacceptable. This represents something of a change from the historical point of view where animals did not have any moral status and the treatment of animals was mostly subservient to maintaining the health and dignity of humans [ 36 ].

Animal rights advocates strongly argue that the moral status of non-human animals is similar to that of humans, and that animals are entitled to equality of treatment. In this view, animals should be treated with the same level of respect as humans, and no one should have the right to force them into any service or to kill them or use them for their own goals. One aspect of this argument claims that moral status depends upon the capacity to suffer or enjoy life [ 37 ].

In terms of suffering and the capacity of enjoying life, many animals are not very different from human beings, as they can feel pain and experience pleasure [ 38 ]. Hence, they should be given the same moral status as humans and deserve equivalent treatment. Supporters of this argument point out that according animals a lower moral status than humans is a type of prejudice known as “speciesism” [ 38 ]. Among humans, it is widely accepted that being a part of a specific race or of a specific gender does not provide the right to ascribe a lower moral status to the outsiders. Many advocates of animal rights deploy the same argument, that being human does not give us sufficient grounds declare animals as being morally less significant [ 36 ].

ARGUMENTS IN FAVOR OF ANIMAL EXPERIMENTATION

Those who support animal experimentation have frequently made the argument that animals cannot be elevated to be seen as morally equal to humans [ 39 ]. Their main argument is that the use of the terms “moral status” or “morality” is debatable. They emphasize that we must not make the error of defining a quality or capacity associated with an animal by using the same adjectives used for humans [ 39 ]. Since, for the most part, animals do not possess humans’ cognitive capabilities and lack full autonomy (animals do not appear to rationally pursue specific goals in life), it is argued that therefore, they cannot be included in the moral community [ 39 ]. It follows from this line of argument that, if animals do not possess the same rights as human beings, their use in research experimentation can be considered appropriate [ 40 ]. The European and the American legislation support this kind of approach as much as their welfare is respected.

Another aspect of this argument is that the benefits to human beings of animal experimentation compensate for the harm caused to animals by these experiments.

In other words, animal harm is morally insignificant compared to the potential benefits to humans. Essentially, supporters of animal experimentation claim that human beings have a higher moral status than animals and that animals lack certain fundamental rights accorded to humans. The potential violations of animal rights during animal research are, in this way, justified by the greater benefits to mankind [ 40 , 41 ]. A way to evaluate when the experiments are morally justified was published in 1986 by Bateson, which developed the Bateson’s Cube [ 42 ]. The Cube has three axes: suffering, certainty of benefit and quality of research. If the research is high-quality, beneficial, and not inflicting suffering, it will be acceptable. At the contrary, painful, low-quality research with lower likelihood of success will not be acceptable [ 42 , 43 ].

Impact of experimentations on animals

Ability to feel pain and distress.

Like humans, animal have certain physical as well as psychological characteristics that make their use for experimentation controversial [ 44 ].

In the last few decades, many studies have increased knowledge of animal awareness and sentience: they indicate that animals have greater potential to experience damage than previously appreciated and that current rights and protections need to be reconsidered [ 45 ]. In recent times, scientists as well as ethicists have broadly acknowledged that animals can also experience distress and pain [ 46 ]. Potential sources of such harm arising from their use in research include disease, basic physiological needs deprivation and invasive procedures [ 46 ]. Moreover, social deprivation and lack of the ability to carry out their natural behaviors are other causes of animal harm [ 46 ]. Several studies have shown that, even in response to very gentle handling and management, animals can show marked alterations in their physiological and hormonal stress markers [ 47 ].

In spite of the fact that suffering and pain are personalized experiences, several multi-disciplinary studies have provided clear evidence of animals experiencing pain and distress. In particular, some animal species have the ability to express pain similarly to human due to common psychological, neuroanatomical and genetic characteristics [ 48 ]. Similarly, animals share a resemblance to humans in their developmental, genetic and environmental risk factors for psychopathology. For instance, in many species, it has been shown that fear operates within a less organized subcortical neural circuit than pain [ 49 , 50 ]. Various types of depression and anxiety disorders like posttraumatic stress disorder have also been reported in mammals [ 51 ].

PSYCHOLOGICAL CAPABILITIES OF ANIMALS

Some researchers have suggested that besides their ability to experience physical and psychological pain and distress, some animals also exhibit empathy, self-awareness and language-like capabilities. They also demonstrate tools-linked cognizance, pleasure-seeking and advanced problem-solving skills [ 52 ]. Moreover, mammals and birds exhibit playful behavior, an indicator of the capacity to experience pleasure. Other taxa such as reptiles, cephalopods and fishes have also been observed to display playful behavior, therefore the current legislation prescribes the use of environmental enrichers [ 53 ]. The presence of self-awareness ability, as assessed by mirror self-recognition, has been reported in magpies, chimpanzees and other apes, and certain cetaceans [ 54 ]. Recently, another study has revealed that crows have the ability to create and use tools that involve episodic-like memory formation and its retrieval. From these findings, it may be suggested that crows as well as related species show evidence of flexible learning strategies, causal reasoning, prospection and imagination that are similar to behavior observed in great apes [ 55 ]. In the context of resolving the ethical dilemmas about animal experimentation, these observations serve to highlight the challenges involved [ 56 , 57 ].

Ethics, principles and legislation in animal experimentation

Ethics in animal experimentation.

Legislation around animal research is based on the idea of the moral acceptability of the proposed experiments under specific conditions [ 58 ]. The significance of research ethics that ensures proper treatment of experimental animals [ 58 ]. To avoid undue suffering of animals, it is important to follow ethical considerations during animal studies [ 1 ]. It is important to provide best human care to these animals from the ethical and scientific point of view [ 1 ]. Poor animal care can lead to experimental outcomes [ 1 ]. Thus, if experimental animals mistreated, the scientific knowledge and conclusions obtained from experiments may be compromised and may be difficult to replicate, a hallmark of scientific research [ 1 ]. At present, most ethical guidelines work on the assumption that animal experimentation is justified because of the significant potential benefits to human beings. These guidelines are often permissive of animal experimentation regardless of the damage to the animal as long as human benefits are achieved [ 59 ].

PRINCIPLE OF THE 4 RS

Although animal experimentation has resulted in many discoveries and helped in the understanding numerous aspects of biological science, its use in various sectors is strictly controlled. In practice, the proposed set of animal experiments is usually considered by a multidisciplinary Ethics Committee before work can commence [ 60 ]. This committee will review the research protocol and make a judgment as to its sustainability. National and international laws govern the utilization of animal experimentation during research and these laws are mostly based on the universal doctrine presented by Russell and Burch (1959) known as principle of the 3 Rs. The 3Rs referred to are Reduction, Refinement and Replacement, and are applied to protocols surrounding the use of animals in research. Some researchers have proposed another “R”, of responsibility for the experimental animal as well as for the social and scientific status of the animal experiments [ 61 ]. Thus, animal ethics committees commonly review research projects with reference to the 4 Rs principles [ 62 ].

The first “R”, Reduction means that the experimental design is examined to ensure that researchers have reduced the number of experimental animals in a research project to the minimum required for reliable data [ 59 ]. Methods used for this purpose include improved experimental design, extensive literature search to avoid duplication of experiments [ 35 ], use of advanced imaging techniques, sharing resources and data, and appropriate statistical data analysis that reduce the number of animals needed for statistically significant results [ 2 , 63 ].

The second “R”, Refinement involves improvements in procedure that minimize the harmful effects of the proposed experiments on the animals involved, such as reducing pain, distress and suffering in a manner that leads to a general improvement in animal welfare. This might include for example improved living conditions for research animals, proper training of people handling animals, application of anesthesia and analgesia when required and the need for euthanasia of the animals at the end of the experiment to curtail their suffering [ 63 ].

The third “R”, Replacement refers to approaches that replace or avoid the use of experimental animals altogether. These approaches involve use of in silico methods/computerized techniques/software and in vitro methods like cell and tissue culture testing, as well as relative replacement methods by use of invertebrates like nematode worms, fruit flies and microorganisms in place of vertebrates and higher animals [ 1 ]. Examples of proper application of these first “3R2 principles are the use of alternative sources of blood, the exploitation of commercially used animals for scientific research, a proper training without use of animals and the use of specimen from previous experiments for further researches [ 64-67 ].

The fourth “R”, Responsibility refers to concerns around promoting animal welfare by improvements in experimental animals’ social life, development of advanced scientific methods for objectively determining sentience, consciousness, experience of pain and intelligence in the animal kingdom, as well as effective involvement in the professionalization of the public discussion on animal ethics [ 68 ].

OTHER ASPECTS OF ANIMAL RESEARCH ETHICS

Other research ethics considerations include having a clear rationale and reasoning for the use of animals in a research project. Researchers must have reasonable expectation of generating useful data from the proposed experiment. Moreover, the research study should be designed in such a way that it should involve the lowest possible sample size of experimental animals while producing statistically significant results [ 35 ].

All individual researchers that handle experimental animals should be properly trained for handling the particular species involved in the research study. The animal’s pain, suffering and discomfort should be minimized [ 69 ]. Animals should be given proper anesthesia when required and surgical procedures should not be repeated on same animal whenever possible [ 69 ]. The procedure of humane handling and care of experimental animals should be explicitly detailed in the research study protocol. Moreover, whenever required, aseptic techniques should be properly followed [ 70 ]. During the research, anesthetization and surgical procedures on experimental animals should only be performed by professionally skilled individuals [ 69 ].

The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines that are issued by the National Center for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) are designed to improve the documentation surrounding research involving experimental animals [ 70 ]. The checklist provided includes the information required in the various sections of the manuscript i.e. study design, ethical statements, experimental procedures, experimental animals and their housing and husbandry, and more [ 70 ].

It is critical to follow the highest ethical standards while performing animal experiments. Indeed, most of the journals refuse to publish any research data that lack proper ethical considerations [ 35 ].

INVESTIGATORS’ ETHICS

Since animals have sensitivity level similar to the human beings in terms of pain, anguish, survival instinct and memory, it is the responsibility of the investigator to closely monitor the animals that are used and identify any sign of distress [ 71 ]. No justification can rationalize the absence of anesthesia or analgesia in animals that undergo invasive surgery during the research [ 72 ]. Investigators are also responsible for giving high-quality care to the experimental animals, including the supply of a nutritious diet, easy water access, prevention of and relief from any pain, disease and injury, and appropriate housing facilities for the animal species [ 73 ]. A research experiment is not permitted if the damage caused to the animal exceeds the value of knowledge gained by that experiment. No scientific advancement based on the destruction and sufferings of another living being could be justified. Besides ensuring the welfare of animals involved, investigators must also follow the applicable legislation [ 74 , 75 ].

To promote the comfort of experimental animals in England, an animal protection society named: ‘The Society for the Preservation of Cruelty to Animals’ (now the Royal Society for the Prevention of Cruelty to Animals) was established (1824) that aims to prevent cruelty to animal [ 76 ].

ANIMAL WELFARE LAWS

Legislation for animal protection during research has long been established. In 1876 the British Parliament sanctioned the ‘Cruelty to Animals Act’ for animal protection. Russell and Burch (1959) presented the ‘3 Rs’ principles: Replacement, Reduction and Refinement, for use of animals during research [ 61 ]. Almost seven years later, the U.S.A also adopted regulations for the protection of experimental animals by enacting the Laboratory Animal Welfare Act of 1966 [ 60 ]. In Brazil, the Arouca Law (Law No. 11,794/08) regulates the animal use in scientific research experiments [ 76 ].

These laws define the breeding conditions, and regulate the use of animals for scientific research and teaching purposes. Such legal provisions control the use of anesthesia, analgesia or sedation in experiments that could cause distress or pain to experimental animals [ 59 , 76 ]. These laws also stress the need for euthanasia when an experiment is finished, or even during the experiment if there is any intense suffering for the experimental animal [ 76 ].

Several national and international organizations have been established to develop alternative techniques so that animal experimentation can be avoided, such as the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) ( www.caat.jhsph.edu ), the European Centre for the Validation of Alternative Methods (ECVAM) [ 77 ], the Universities Federation for Animal Welfare (UFAW) ( www.ufaw.org.uk ), The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) [ 78 ], and The Center for Alternatives to Animal Testing (CAAT) ( www.caat.jhsph.edu ). The Brazilian ‘Arouca Law’ also constitutes a milestone, as it has created the ‘National Council for the Control of Animal Experimentation’ (CONCEA) that deals with the legal and ethical issues related to the use of experimental animals during scientific research [ 76 ].

Although national as well as international laws and guidelines have provided basic protections for experimental animals, the current regulations have some significant discrepancies. In the U.S., the Animal Welfare Act excludes rats, mice and purpose-bred birds, even though these species comprise almost 90% of the animals that are used for research purpose [ 79 ]. On the other hand, certain cats and dogs are getting special attention along with extra protection. While the U.S. Animal Welfare Act ignores birds, mice and rats, the U.S. guidelines that control research performed using federal funding ensure protections for all vertebrates [ 79 , 80 ].

Living conditions of animals

Choice of the animal model.

Based on all the above laws and regulations and in line with the deliberations of ethical committees, every researcher must follow certain rules when dealing with animal models.

Before starting any experimental work, thorough research should be carried out during the study design phase so that the unnecessary use of experimental animals is avoided. Nevertheless, certain research studies may have compelling reasons for the use of animal models, such as the investigation of human diseases and toxicity tests. Moreover, animals are also widely used in the training of health professionals as well as in training doctors in surgical skills [ 1 , 81 ].

Researcher should be well aware of the specific traits of the animal species they intend to use in the experiment, such as its developmental stages, physiology, nutritional needs, reproductive characteristics and specific behaviors. Animal models should be selected on the basis of the study design and the biological relevance of the animal [ 1 ].

Typically, in early research, non-mammalian models are used to get rapid insights into research problems such as the identification of gene function or the recognition of novel therapeutic options. Thus, in biomedical and biological research, among the most commonly used model organisms are the Zebrafish, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans . The main advantage of these non-mammalian animal models is their prolific reproducibility along with their much shorter generation time. They can be easily grown in any laboratory setting, are less expensive than the murine animal models and are somewhat more powerful than the tissue and cell culture approaches [ 82 ].

Caenorhabditis elegans is a small-sized nematode with a short life cycle and that exists in large populations and is relatively inexpensive to cultivate. Scientists have gathered extensive knowledge of the genomics and genetics of Caenorhabditis elegans ; but Caenorhabditis elegans models, while very useful in some respects, are unable to represent all signaling pathways found in humans. Furthermore, due to its short life cycle, scientists are unable to investigate long term effects of test compounds or to analyze primary versus secondary effects [ 6 ].

Similarly, the fruit fly Drosophila melanogaster has played a key role in numerous biomedical discoveries. It is small in size, has a short life cycle and large population size, is relatively inexpensive to breed, and extensive genomics and genetics information is available [ 6 ]. However, its respiratory, cardiovascular and nervous systems differ considerably from human beings. In addition, its immune system is less developed when compared to vertebrates, which is why effectiveness of a drug in Drosophila melanogaster may not be easily extrapolated to humans [ 83 ].

The Zebrafish ( Danio rerio ) is a small freshwater teleost, with transparent embryos, providing easy access for the observation of organogenesis and its manipulation. Therefore, Zebrafish embryos are considered good animal models for different human diseases like tuberculosis and fetal alcohol syndrome and are useful as neurodevelopmental research models. However, Zebrafish has very few mutant strains available, and its genome has numerous duplicate genes making it impossible to create knockout strains, since disrupting one copy of the gene will not disrupt the second copy of that gene. This feature limits the use of Zebrafish as animal models to study human diseases. Additionally they are rather expensive, have long life cycle, and genomics and genetics studies are still in progress [ 82 , 84 ].

Thus, experimentation on these three animals might not be equivalent to experimentation on mammals. Mammalian animal model are most similar to human beings, so targeted gene replacement is possible. Traditionally, mammals like monkey and mice have been the preferred animal models for biomedical research because of their evolutionary closeness to humans. Rodents, particularly mice and rats, are the most frequently used animal models for scientific research. Rats are the most suitable animal model for the study of obesity, shock, peritonitis, sepsis, cancer, intestinal operations, spleen, gastric ulcers, mononuclear phagocytic system, organ transplantations and wound healing. Mice are more suitable for studying burns, megacolon, shock, cancer, obesity, and sepsis as mentioned previously [ 85 ].

Similarly, pigs are mostly used for stomach, liver and transplantation studies, while rabbits are suitable for the study of immunology, inflammation, vascular biology, shock, colitis and transplantations. Thus, the choice of experimental animal mainly depends upon the field of scientific research under consideration [ 1 ].

HOUSING AND ENVIRONMENTAL ENRICHMENT

Researchers should be aware of the environment and conditions in which laboratory animals are kept during research, and they also need to be familiar with the metabolism of the animals kept in vivarium, since their metabolism can easily be altered by different factors such as pain, stress, confinement, lack of sunlight, etc. Housing conditions alter animal behavior, and this can in turn affect experimental results. By contrast, handling procedures that feature environmental enrichment and enhancement help to decrease stress and positively affect the welfare of the animals and the reliability of research data [ 74 , 75 ].

In animals, distress- and agony-causing factors should be controlled or eliminated to overcome any interference with data collection as well as with interpretation of the results, since impaired animal welfare leads to more animal usage during experiment, decreased reliability and increased discrepancies in results along with the unnecessary consumption of animal lives [ 86 ].

To reduce the variation or discrepancies in experimental data caused by various environmental factors, experimental animals must be kept in an appropriate and safe place. In addition, it is necessary to keep all variables like humidity, airflow and temperature at levels suitable for those species, as any abrupt variation in these factors could cause stress, reduced resistance and increased susceptibility to infections [ 74 ].

The space allotted to experimental animals should permit them free movement, proper sleep and where feasible allow for interaction with other animals of the same species. Mice and rats are quite sociable animals and must, therefore, be housed in groups for the expression of their normal behavior. Usually, laboratory cages are not appropriate for the behavioral needs of the animals. Therefore, environmental enrichment is an important feature for the expression of their natural behavior that will subsequently affect their defense mechanisms and physiology [ 87 ].

The features of environmental enrichment must satisfy the animals’ sense of curiosity, offer them fun activities, and also permit them to fulfill their behavioral and physiological needs. These needs include exploring, hiding, building nests and gnawing. For this purpose, different things can be used in their environment, such as PVC tubes, cardboard, igloos, paper towel, cotton, disposable masks and paper strips [ 87 ].

The environment used for housing of animals must be continuously controlled by appropriate disinfection, hygiene protocols, sterilization and sanitation processes. These steps lead to a reduction in the occurrence of various infectious agents that often found in vivarium, such as Sendai virus, cestoda and Mycoplasma pulmonis [ 88 ].

Euthanasia is a term derived from Greek, and it means a death without any suffering. According to the Brazilian Arouca Law (Article 14, Chapter IV, Paragraphs 1 and 2), an animal should undergo euthanasia, in strict compliance with the requirements of each species, when the experiment ends or during any phase of the experiment, wherever this procedure is recommended and/or whenever serious suffering occurs. If the animal does not undergo euthanasia after the intervention it may leave the vivarium and be assigned to suitable people or to the animal protection bodies, duly legalized [ 1 ].

Euthanasia procedures must result in instant loss of consciousness which leads to respiratory or cardiac arrest as well as to complete brain function impairment. Another important aspect of this procedure is calm handling of the animal while taking it out of its enclosure, to reduce its distress, suffering, anxiety and fear. In every research project, the study design should include the details of the appropriate endpoints of these experimental animals, and also the methods that will be adopted. It is important to determine the appropriate method of euthanasia for the animal being used. Another important point is that, after completing the euthanasia procedure, the animal’s death should be absolutely confirmed before discarding their bodies [ 87 , 89 ].

Relevance of animal experimentations and possible alternatives

Relevance of animal experiments and their adverse effects on human health.

One important concern is whether human diseases, when inflicted on experimental animals, adequately mimic the progressions of the disease and the treatment responses observed in humans. Several research articles have made comparisons between human and animal data, and indicated that the results of animals’ research could not always be reliably replicated in clinical research among humans. The latest systematic reviews about the treatment of different clinical conditions including neurology, vascular diseases and others, have established that the results of animal studies cannot properly predict human outcomes [ 59 , 90 ].

At present, the reliability of animal experiments for extrapolation to human health is questionable. Harmful effects may occur in humans because of misleading results from research conducted on animals. For instance, during the late fifties, a sedative drug, thalidomide, was prescribed for pregnant women, but some of the women using that drug gave birth to babies lacking limbs or with foreshortened limbs, a condition called phocomelia. When thalidomide had been tested on almost all animal models such as rats, mice, rabbits, dogs, cats, hamsters, armadillos, ferrets, swine, guinea pig, etc., this teratogenic effect was observed only occasionally [ 91 ]. Similarly, in 2006, the compound TGN 1412 was designed as an immunomodulatory drug, but when it was injected into six human volunteer, serious adverse reactions were observed resulting from a deadly cytokine storm that in turn led to disastrous systemic organ failure. TGN 1412 had been tested successfully in rats, mice, rabbits, and non-human primates [ 92 ]. Moreover, Bailey (2008) reported 90 HIV vaccines that had successful trial results in animals but which failed in human beings [ 93 ]. Moreover, in Parkinson disease, many therapeutic options that have shown promising results in rats and non-human primate models have proved harmful in humans. Hence, to analyze the relevance of animal research to human health, the efficacy of animal experimentation should be examined systematically [ 94 , 95 ]. At the same time, the development of hyperoxaluria and renal failure (up to dialysis) after ileal-jejunal bypass was unexpected because this procedure was not preliminarily evaluated on an animal model [ 96 ].

Several factors play a role in the extrapolation of animal-derived data to humans, such as environmental conditions and physiological parameters related to stress, age of the experimental animals, etc. These factors could switch on or off genes in the animal models that are specific to species and/or strains. All these observations challenge the reliability and suitability of animal experimentation as well as its objectives with respect to human health [ 76 , 92 ].

ALTERNATIVE TO ANIMAL EXPERIMENTATION/DEVELOPMENT OF NEW PRODUCTS AND TECHNIQUES TO AVOID ANIMAL SACRIFICE IN RESEARCH

Certainly, in vivo animal experimentation has significantly contributed to the development of biological and biomedical research. However it has the limitations of strict ethical issues and high production cost. Some scientists consider animal testing an ineffective and immoral practice and therefore prefer alternative techniques to be used instead of animal experimentation. These alternative methods involve in vitro experiments and ex vivo models like cell and tissue cultures, use of plants and vegetables, non-invasive human clinical studies, use of corpses for studies, use of microorganisms or other simpler organism like shrimps and water flea larvae, physicochemical techniques, educational software, computer simulations, mathematical models and nanotechnology [ 97 ]. These methods and techniques are cost-effective and could efficiently replace animal models. They could therefore, contribute to animal welfare and to the development of new therapies that can identify the therapeutics and related complications at an early stage [ 1 ].

The National Research Council (UK) suggested a shift from the animal models toward computational models, as well as high-content and high-throughput in vitro methods. Their reports highlighted that these alternative methods could produce predictive data more affordably, accurately and quickly than the traditional in vivo or experimental animal methods [ 98 ].

Increasingly, scientists and the review boards have to assess whether addressing a research question using the applied techniques of advanced genetics, molecular, computational and cell biology, and biochemistry could be used to replace animal experiments [ 59 ]. It must be remembered that each alternative method must be first validated and then registered in dedicated databases.

An additional relevant concern is how precisely animal data can mirror relevant epigenetic changes and human genetic variability. Langley and his colleagues have highlighted some of the examples of existing and some emerging non-animal based research methods in the advanced fields of neurology, orthodontics, infectious diseases, immunology, endocrine, pulmonology, obstetrics, metabolism and cardiology [ 99 ].

IN SILICO SIMULATIONS AND INFORMATICS

Several computer models have been built to study cardiovascular risk and atherosclerotic plaque build-up, to model human metabolism, to evaluate drug toxicity and to address other questions that were previously approached by testing in animals [ 100 ].

Computer simulations can potentially decrease the number of experiments required for a research project, however simulations cannot completely replace laboratory experiments. Unfortunately, not all the principles regulating biological systems are known, and computer simulation provide only an estimation of possible effects due to the limitations of computer models in comparison with complex human tissues. However, simulation and bio-informatics are now considered essential in all fields of science for their efficiency in using the existing knowledge for further experimental designs [ 76 ].

At present, biological macromolecules are regularly simulated at various levels of detail, to predict their response and behavior under certain physical conditions, chemical exposures and stimulations. Computational and bioinformatic simulations have significantly reduced the number of animals sacrificed during drug discovery by short listing potential candidate molecules for a drug. Likewise, computer simulations have decreased the number of animal experiments required in other areas of biological science by efficiently using the existing knowledge. Moreover, the development of high definition 3D computer models for anatomy with enhanced level of detail, it may make it possible to reduce or eliminate the need for animal dissection during teaching [ 101 , 102 ].

3D CELL-CULTURE MODELS AND ORGANS-ON-CHIPS

In the current scenario of rapid advancement in the life sciences, certain tissue models can be built using 3D cell culture technology. Indeed, there are some organs on micro-scale chip models used for mimicking the human body environment. 3D models of multiple organ systems such as heart, liver, skin, muscle, testis, brain, gut, bone marrow, lungs and kidney, in addition to individual organs, have been created in microfluidic channels, re-creating the physiological chemical and physical microenvironments of the body [ 103 ]. These emerging techniques, such as the biomedical/biological microelectromechanical system (Bio-MEMS) or lab-on-a-chip (LOC) and micro total analysis systems (lTAS) will, in the future, be a useful substitute for animal experimentation in commercial laboratories in the biotechnology, environmental safety, chemistry and pharmaceutical industries. For 3D cell culture modeling, cells are grown in 3D spheroids or aggregates with the help of a scaffold or matrix, or sometimes using a scaffold-free method. The 3D cell culture modeling conditions can be altered to add proteins and other factors that are found in a tumor microenvironment, for example, or in particular tissues. These matrices contain extracellular matrix components such as proteins, glycoconjugates and glycosaminoglycans that allow for cell communication, cell to cell contact and the activation of signaling pathways in such a way that the morphological and functional differentiation of these cells can accurately mimic their environment in vivo . This methodology, in time, will bridge the gap between in vivo and in vitro drug screening, decreasing the utilization of animal models during research [ 104 ].

ALTERNATIVES TO MICROBIAL CULTURE MEDIA AND SERUM-FREE ANIMAL CELL CULTURES

There are moves to reduce the use of animal derived products in many areas of biotechnology. Microbial culture media peptones are mostly made by the proteolysis of farmed animal meat. However, nowadays, various suppliers provide peptones extracted from yeast and plants. Although the costs of these plant-extracted peptones are the same as those of animal peptones, plant peptones are more environmentally favorable since less plant material and water are required for them to grow, compared with the food grain and fodder needed for cattle that are slaughtered for animal peptone production [ 105 ].

Human cell culture is often carried out in a medium that contains fetal calf serum, the production of which involves animal (cow) sacrifice or suffering. In fact, living pregnant cows are used and their fetuses removed to harvest the serum from the fetal blood. Fetal calf serum is used because it is a natural medium rich in all the required nutrients and significantly increases the chances of successful cell growth in culture. Scientists are striving to identify the factors and nutrients required for the growth of various types of cells, with a view to eliminating the use of calf serum. At present, most cell lines could be cultured in a chemically-synthesized medium without using animal products. Furthermore, data from chemically-synthesized media experiments may have better reproducibility than those using animal serum media, since the composition of animal serum does change from batch to batch on the basis of animals’ gender, age, health and genetic background [ 76 ].

ALTERNATIVES TO ANIMAL-DERIVED ANTIBODIES

Animal friendly affinity reagents may act as an alternative to antibodies produced, thereby removing the need for animal immunization. Typically, these antibodies are obtained in vitro by yeast, phage or ribosome display. In a recent review, a comparative analysis between animal friendly affinity reagents and animal derived-antibodies showed that the affinity reagents have superior quality, are relatively less time consuming, have more reproducibility and are more reliable and are cost-effective [ 106 , 107 ].

Conclusions

Animal experimentation led to great advancement in biological and biomedical sciences and contributed to the discovery of many drugs and treatment options. However, such experimentation may cause harm, pain and distress to the animals involved. Therefore, to perform animal experimentations, certain ethical rules and laws must be strictly followed and there should be proper justification for using animals in research projects. Furthermore, during animal experimentation the 4 Rs principles of reduction, refinement, replacement and responsibility must be followed by the researchers. Moreover, before beginning a research project, experiments should be thoroughly planned and well-designed, and should avoid unnecessary use of animals. The reliability and reproducibility of animal experiments should also be considered. Whenever possible, alternative methods to animal experimentation should be adopted, such as in vitro experimentation, cadaveric studies, and computer simulations.

While much progress has been made on reducing animal experimentation there is a need for greater awareness of alternatives to animal experiments among scientists and easier access to advanced modeling technologies. Greater research is needed to define a roadmap that will lead to the elimination of all unnecessary animal experimentation and provide a framework for adoption of reliable alternative methodologies in biomedical research.

Acknowledgements

This research was funded by the Provincia Autonoma di Bolzano in the framework of LP 15/2020 (dgp 3174/2021).

Conflicts of interest statement

Authors declare no conflict of interest.

Author's contributions

MB: study conception, editing and critical revision of the manuscript; AKK, DP, GH, RB, Paul S, Peter S, RM, BF, NC, SM, LL, DD, GMT, MCE, MD, SM, Daniele M, GB, AD, KD, MCM, TB, MS, STC, Donald M, AM, AB, KLH, MK, LS, LL, GF: literature search, editing and critical revision of the manuscript. All authors have read and approved the final manuscript.

Contributor Information

INTERNATIONAL BIOETHICS STUDY GROUP : Derek Pheby , Gary Henehan , Richard Brown , Paul Sieving , Peter Sykora , Robert Marks , Benedetto Falsini , Natale Capodicasa , Stanislav Miertus , Lorenzo Lorusso , Gianluca Martino Tartaglia , Mahmut Cerkez Ergoren , Munis Dundar , Sandro Michelini , Daniele Malacarne , Tommaso Beccari , Michele Samaja , Matteo Bertelli , Donald Martin , Assunta Morresi , Ariola Bacu , Karen L. Herbst , Mykhaylo Kapustin , Liborio Stuppia , Ludovica Lumer , and Giampietro Farronato

Ethics of Medical Research with Animals

The Case for Phasing Out Experiments on Primates

Whether they realize it or not, most stakeholders in the debate about using animals for research agree on the common goal of seeking an end to research that causes animals harm. [1]  The central issues in the controversy are about how much effort should be devoted to that goal and when we might reasonably expect to achieve it. Some progress has already been made: The number of animals used for research is about half what it was in the 1970s, and biomedical research has reached the point where we can reasonably begin to envision a time when it could advance without causing harm to animals. With some effort and aggressive development of new biomedical research technologies, full replacement of animals in harmful research is within our grasp. The goal will not be reached all at once, however, and phasing out invasive research on all nonhuman primates should be the priority.

Approximately 70,000 nonhuman primates are used for research in the United States each year, according to the U.S. Department of Agriculture, and another 45,000 are held or bred for research. They include macaques, baboons, marmosets, and other monkeys, as well as some chimpanzees. Moreover, these numbers are increasing in the United States and Canada. The rise is driven in part by the “high-fidelity” notion (supported by very little careful scientific justification) that primates are likely to be better models than mice and rats for studying human diseases, and partly by the sheer availability of primates.

The availability factor is a result of historical accident. In the 1960s, the United States invested in a significant infrastructure for primate research through creation of the National Primate Research Centers. The primate center program was the result of two unrelated occurrences. First, in the 1950s, hundreds of thousands of wild primates were captured and imported to support the race to develop a poliomyelitis vaccine. By 1960, with polio vaccines in use, this “race” was essentially over, but laboratories still had tens of thousands of primates. Then, they became swept up in another kind of race. The Russians had beaten the United States into space by launching the first satellite, creating panic that Russian science was outpacing U.S. science. American scientists made the argument that, because the Russians had a big primate research center, the United States should also have one or more primate centers. Seven facilities, formally recognized as government-supported institutions, were set up to provide support for and opportunities to do research in nonhuman primates.

The centers did not produce the hoped-for results. Three federal assessments found that the research conducted by the centers fell far short of expectations in terms of quality, and many deficiencies were also noted. [2]  In the early 1980s, these centers were “rescued,” in a sense, by the discovery that primates at the California Regional Primate Research Center were suffering from a simian version of AIDS. Suddenly, there was renewed focus on research in nonhuman primates. There are now eight National Primate Research Centers, the objective of which continues to be “to provide support for scientists who use NHPs in their research.” [3]

Primates are used for a wide variety of research purposes. An analysis of one thousand federally funded studies that involved nonhuman primates found that research on HIV accounted for about 27 percent of the funding, followed by colony maintenance (likely because caring for primates is costly) at 15 percent, neurological research at 14 percent, and developmental research at 10 percent. [4]

Arguments for Phasing Out Primate Research

Phasing out primate use should be a priority for ethical, scientific, and economic reasons. The ethical concerns fall into two categories. One of them is the nature of the primates themselves. They are well known for their cognitive and emotional abilities. Studies demonstrate that they have mathematical, memory, and problem-solving skills and that they experience emotions similar to those of humans—for example, depression, anxiety, and joy. Chimpanzees can learn human languages, such as American Sign Language. Primates also have very long lifespans, which is an ethical issue because they are typically held in laboratories for decades and experimented on repeatedly.  The other category of ethical concern is how primates are treated. Each year, thousands are captured from the wild, mostly in Asia and Mauritius, and transported to other countries. For example, China sets up breeding colonies, and the infants are sold to various countries, including the United States and European countries.  The animals experience considerable stress, such as days of transport in small crates and restrictions on food and water intake. Studies show that it takes months for their physiological systems to return to baseline levels, [5]  and then they face the trauma of research, including infection with virulent diseases, social isolation, food and water deprivation, withdrawal from drugs, and repeated surgeries.

Providing for the welfare of primates in a laboratory setting is very challenging. According to the Animal Welfare Act, each facility must develop and follow a plan for environmental enhancement to promote the psychological well-being of nonhuman primates. The plan must address social grouping; enriching the environment, with special consideration for great apes; caring for infants, young juveniles, and those primates showing signs of psychological distress; and ensuring the well-being of those primates who are used in a protocol requiring restricted activity.

Social companionship is the most important psychological factor for most primates. Federal law requires institutions to house primates in groups unless there is justification, such as debilitation as a result of age or other conditions, for housing them alone. But a recent analysis of documents from two large facilities obtained by The Humane Society of the United States demonstrates that primates spent an average of 53 percent of their lives housed alone. In many instances, a metal shape hung for a month on the bars of a metal cage was deemed to constitute adequate “enrichment.” [6]

As we have done with chimpanzees, we need to critically analyze uses of other nonhuman primates. A good starting point would be the formation of a working group  of diverse stakeholders who agree that ending primate research is a worthwhile goal.

The Bateson report recommended that all proposed primate studies be assessed using the following parameters: scientific value, probability of medical or other benefit, availability of alternatives, and likelihood and extent of animal suffering. [9]   The report indicated that if a proposed use would cause severe suffering, it should be allowed only if there is a high likelihood of benefit. The report considered approximately 9 percent of the studies it examined to be of low importance and to inflict high levels of suffering. [10]  The report was critical of some of the neuroscience research, which represented nearly half of the research surveyed. It found that half of the thirty-one neuroscience studies took a high toll on animal welfare, although most were also considered to be of high scientific value. Two of the studies were of concern because they posed a “high welfare impact,” but moderate-quality science and little medical benefit. [11]  The report recommended that more consideration be given to alternatives to nonhuman primates, including brain imaging, noninvasive electrophysiological technologies, in vitro and in silico techniques, and even research on human subjects. [12]  The report recommended other ways of reducing the number of primates needed for research, including data sharing, publication of all results, and periodic review of outcomes, benefits, and impact of the research. “Researchers using NHPs have a moral obligation to publish results—even if negative—in order to prevent work from being repeated unnecessarily,” the report states. [13]

In addition to the ethical and scientific arguments for ending research involving primates, there are economic reasons. Primates are very expensive to maintain. The eight National Primate Research Centers alone receive $1 billion of the National Institutes of Health’s total $32 billion budget. The care and upkeep of primates other than chimpanzees is twenty to twenty-five dollars per day, compared with twenty cents to about $1.60 per day for small rodents. We argue that much of the research with nonhuman primates is either of questionable value or has not been carefully evaluated and justified. Therefore, these funds might be better spent on other research models, including several technologies that could replace nonhuman primates and other animals. Francis Collins, director of the NIH, argued in 2011 that new high-throughput approaches could overcome the drawbacks of animal models—they are slow, expensive, and not sufficiently relevant to human biology and pharmacology. [14]

Several such technologies are available. The U.S. Army recently announced that it would end the use of monkeys for chemical casualty training courses and replace them with alternatives such as simulators that mimic the effects of nerve gas on victims. [15]

Following Chimpanzees

The process that culminated in the phasing out of invasive research on chimpanzees in the United States in 2011 can and should be applied to all other nonhuman primates. Public opinion and ethical challenges drove that process. Even before the 2011 IOM report, scientists in the United States were having difficulty justifying why they should perform experiments on chimpanzees when their colleagues in other countries had stopped doing so. Unlike nonhuman primates in general, the number of chimpanzees in U.S. labs has been declining since reaching its peak in the late 1990s.

The main drivers for efforts to phase out research on chimpanzees are their genetic, biological, and behavioral similarities with humans. [16]  Chimpanzees are humans’ closest relative. Chimpanzee cognition has been studied extensively, and their capabilities are considerable. As with other primates, the impact of laboratory life—including barren housing and social isolation—on chimpanzees can last decades due to their long lifespan and thus raises significant welfare concerns. There is evidence that some chimpanzees used in research suffer from a form of posttraumatic stress disorder similar to that of humans. In their 2008 article, Gay Bradshaw and colleagues described the plight of a chimpanzee named Jeannie who endured invasive research and social isolation for over a decade. She exhibited abnormal behavior, including self-injury, bouts of aggression, and, according to laboratory documentation, a “nervous breakdown.” When retired to a sanctuary, she recovered partially, but was ultimately diagnosed with complex PTSD. The paper concluded: “The costs of laboratory-caused trauma are immeasurable in their life-long psychological impact on, and consequent suffering of, chimpanzees.” [17]

As we have done with chimpanzees, we need to critically analyze current uses of other nonhuman primates, the viability of alternative models, and the economic issues involved to forge the best way forward. A good starting point would be the formation of a working group of diverse stakeholders who agree that ending primate research is a worthwhile goal. Such a working group—possibly organized by the NIH and the National Academies—would analyze the necessity of primate use and identify existing and potential alternatives.

The stakeholder group could develop a concrete plan to work on common-ground issues. This would involve developing priorities, short-term outcomes, and related activities. The ongoing Human Toxicology Project Consortium’s work to ultimately replace all animals for toxicity testing is a good example of this approach. (See “No Animals Harmed:  Toward a Paradigm Shift in Toxicity Testing,” in this volume.) The mission of the consortium is to “serve as a catalyst for the prompt, global, and coordinated implementation of ‘21 st Century’ toxicology, which will better safeguard human health and hasten the replacement of animal use in toxicology.” [18]   Because science is ever-changing, there must be an ongoing analysis of new technologies and challenges, and regulatory authorities must adjust regulations accordingly. In the United States, many stakeholders express frustration with the fact that the Food and Drug Administration, for example, favors data from outdated tests, including those that involve primates and other animals.

Phasing out invasive research on all nonhuman primates would take courage on the part of leaders in science and policy. It is a formidable task, but similarly transformative changes in how we conduct biomedical research have been achieved. At various points in the past century and a quarter, restrictions have been placed on particular kinds of human and animal research because of ethical issues, despite objections that such restrictions would slow scientific progress; think, for instance, of the Helsinki Declaration to protect human subjects in research and the animal welfare laws in the United States and the European Union. However, these laws have not slowed the pace of discovery about biology and disease processes. If anything, there has been an acceleration of such discovery in the half-century since these restrictions went into effect.

In the early 1950s, Sir Peter Medawar pressed the Universities Federation for Animal Welfare to develop a report on how laboratory animal welfare could be improved and how distress and suffering in the research laboratory might be reduced. That initiative led to publication of a volume on humane experimental approach that is now regarded as the foundation for the concept of the Three Rs of replacement, reduction, and refinement of animal studies. [19]  Ten years later, in 1969, Medawar correctly predicted that laboratory animal use would peak within ten years and then start to decline. He argued that animal research would allow researchers to develop the knowledge and understanding that would lead, eventually, to the replacement of animal use in laboratories. In 2010, forty years after Medawar’s prediction, laboratory animal use is approximately 50 percent of what it was in 1970. Francis Collins has pointed to the down sides of animal-based research—that is “time-consuming, costly, and may not accurately predict efficacy in humans.” [20]   He has also suggested that nonanimal technologies might be quicker and more effective in new drug discovery programs. Given the trends and political will, we believe that we could reach Medawar’s prediction of complete replacement by 2050.

Now is the time for an internationally coordinated effort to define a strategy to replace all invasive research on primates. At the very least, we need to move quickly to reverse the increase in laboratory primate use in the United States and Canada. Until replacement is a realistic option, we must reduce the number of primates used and refine studies to reduce their suffering, for the sake of both animal welfare and science.

Kathleen M. Conlee is vice president for animal research issues with The Humane Society of the United States. She worked for several years at a primate breeding and research facility and also worked with great apes in a sanctuary setting. Her current work focuses on the long-term goal of replacing the use of animals in harmful research and testing, the ongoing development of nonanimal alternatives, and the short-term goals of ending invasive chimpanzee research and retiring chimpanzees from laboratories to sanctuaries. 

Andrew N. Rowan is chief scientific officer at The Humane Society of the United States and chief executive officer of The Humane Society International. He has written numerous books and peer-reviewed publications regarding animal research, including a book titled The Animal Research Controversy: Protest, Process and Public Policy (Center for Animals and Public Policy, Tufts University School of Veterinary Medicine, 1995). He is a biochemist in training, and a focus of his career has been promotion of the three Rs in animal research: replacement of nonhuman animals, reduction in number of animals used, and refinement to decrease animal suffering.

[[12]]12. Ibid., 4, 5, 16.[[12]

• 1. C. Blakemore, “Should We Experiment on Animals? Yes,” Telegraph, October 28, 2008. ↵
• 2. A.N. Rowan, Of Mice, Models and Men (Albany: State University of New York Press, 1984). ↵
• 3. Department of Health and Human Services, Funding Opportunity for the National Primate Research Centers, http://grants.nih.gov/grants/guide/pa-files/PAR-11-136.html, accessed July 7, 2011. ↵
• 4. K.M. Conlee, E.H. Hoffeld, and M.L. Stephens, “A Demographic Analysis of Primate Research in the United States,” Alternatives to Laboratory Animals 32, suppl. 1A (2004): 315-22. ↵
• 5. P.E. Honess, P.J. Johnson, and S.E. Wolfensohn, “A Study of Behavioural Responses of Non-Human Primates to Air Transport and Re-Housing,” Laboratory Animals 38,  no. 2 (2004): 119-32; J.M. Kagira et al., “Hematological Changes in Vervet Monkeys ( Chlorocedub aethiops ) during Eight Months’ Adaptation to Captivity,” American Journal of Primatology 69, no. 9 (2007): 1053-63. ↵
• 6. J. Balcombe and K.M. Conlee, “Primate Life in Two American Laboratories,” presentation to the Eighth World Congress on Alternatives and Animal Use in the Life Sciences, held in Montreal, Quebec, Canada, on August 21-25, 2011. ↵
• 7. P. Bateson, A Review of Research Using Nonhuman Primates: A Report of a Panel Chaired by Professor Sir Patrick Bateson, FRS (London and Wiltshire, U.K.: Biotechnology and Biological Sciences Research Council, Medical Research Council, and Wellcome Trust, 2011) http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d =MRC008083; J.A. Smith and K.M. Boyd, eds., The Use of Non-Human Primates in Research and Testing (Leicester, U.K.: British Psychological Society, 2002); D. Weatherall, The Use of Non-Human Primates in Research: A Working Group Report Chaired by Sir David Weatherall FRS FmedSci (London: Academy of Medical Sciences, 2006), http://www.acmedsci.ac.uk/images/project/nhpdownl.pdf. ↵
• 8. Institute of Medicine, Committee on the Use of Chimpanzees in Biomedical and Behavioral Research, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity (Washington, D.C.: National Academies Press, 2011), 4. ↵
• 9. Bateson, A Review of Research Using Nonhuman Primates , 2. ↵
• 10. Ibid., 1. ↵
• 11. Ibid., 12-13. ↵
• 13. Ibid., 3. ↵
• 14. F.S. Collins, “Reengineering Translational Science: The Time Is Right,” Science Translational Medicine 3, no. (2011): 1-6. ↵
• 15. B. Vastag, “Army to Phase Out Animal Nerve-Agent Testing,” Washington Post, October 13, 2011. ↵
• 16. G.W. Bradshaw et al., “Building Inner Sanctuary: Complex PTSD in Chimpanzees,” Journal of Trauma and Dissociation 9, no. 1 (2008): 9-34; J.A. Smith and K.M. Boyd, eds., The Boyd Group Papers on the Use of Non-Human Primates in Research and Testing (Leicester, U.K.: British Psychological Society, 2002). ↵
• 17. Bradshaw et al., “Building Inner Sanctuary,” 31. ↵
• 18. Human Toxicology Project Consortium Web site, http://htpconsortium.wordpress.com/about-2, accessed February 13, 2012. ↵
• 19. W.M.S. Russell and R.L. Burch, The Principles of Humane Experimental Technique (London: Methuen, 1959). ↵
• 20. F.S. Collins, “Reengineering Translational Science,” 3. ↵

This Old Experiment With Mice Led to Bleak Predictions for Humanity’s Future

From the 1950s to the 1970s, researcher John Calhoun gave rodents unlimited food and studied their behavior in overcrowded conditions

Maris Fessenden ; Updated by Rudy Molinek

What does utopia look like for mice and rats? According to a researcher who did most of his work in the 1950s through 1970s, it might include limitless food, multiple levels and secluded little condos. These were all part of John Calhoun’s experiments to study the effects of population density on behavior. But what looked like rodent paradises at first quickly spiraled into out-of-control overcrowding, eventual population collapse and seemingly sinister behavior patterns.

In other words, the mice were not nice.

Working with rats between 1958 and 1962, and with mice from 1968 to 1972, Calhoun set up experimental rodent enclosures at the National Institute of Mental Health’s Laboratory of Psychology. He hoped to learn more about how humans might behave in a crowded future. His first 24 attempts ended early due to constraints on laboratory space. But his 25th attempt at a utopian habitat, which began in 1968, would become a landmark psychological study. According to Gizmodo ’s Esther Inglis-Arkell, Calhoun’s “Universe 25” started when the researcher dropped four female and four male mice into the enclosure.

By the 560th day, the population peaked with over 2,200 individuals scurrying around, waiting for food and sometimes erupting into open brawls. These mice spent most of their time in the presence of hundreds of other mice. When they became adults, those mice that managed to produce offspring were so stressed out that parenting became an afterthought.

“Few females carried pregnancies to term, and the ones that did seemed to simply forget about their babies,” wrote Inglis-Arkell in 2015. “They’d move half their litter away from danger and forget the rest. Sometimes they’d drop and abandon a baby while they were carrying it.”

A select group of mice, which Calhoun called “the beautiful ones,” secluded themselves in protected places with a guard posted at the entry. They didn’t seek out mates or fight with other mice, wrote Will Wiles in Cabinet magazine in 2011, “they just ate, slept and groomed, wrapped in narcissistic introspection.”

Eventually, several factors combined to doom the experiment. The beautiful ones’ chaste behavior lowered the birth rate. Meanwhile, out in the overcrowded common areas, the few remaining parents’ neglect increased infant mortality. These factors sent the mice society over a demographic cliff. Just over a month after population peaked, around day 600, according to Distillations magazine ’s Sam Kean, no baby mice were surviving more than a few days. The society plummeted toward extinction as the remaining adult mice were just “hiding like hermits or grooming all day” before dying out, writes Kean.

Calhoun launched his experiments with the intent of translating his findings to human behavior. Ideas of a dangerously overcrowded human population were popularized by Thomas Malthus at the end of the 18th century with his book An Essay on the Principle of Population . Malthus theorized that populations would expand far faster than food production, leading to poverty and societal decline. Then, in 1968, the same year Calhoun set his ill-fated utopia in motion, Stanford University entomologist Paul Ehrlich published The Population Bomb . The book sparked widespread fears of an overcrowded and dystopic imminent future, beginning with the line, “The battle to feed all of humanity is over.”

Ehrlich suggested that the impending collapse mirrored the conditions Calhoun would find in his experiments. The cause, wrote Charles C. Mann for Smithsonian magazine in 2018, would be “too many people, packed into too-tight spaces, taking too much from the earth. Unless humanity cut down its numbers—soon—all of us would face ‘mass starvation’ on ‘a dying planet.’”

Calhoun’s experiments were interpreted at the time as evidence of what could happen in an overpopulated world. The unusual behaviors he observed—such as open violence, a lack of interest in sex and poor pup-rearing—he dubbed “behavioral sinks.”

After Calhoun wrote about his findings in a 1962 issue of Scientific American , that term caught on in popular culture, according to a paper published in the Journal of Social History . The work tapped into the era’s feeling of dread that crowded urban areas heralded the risk of moral decay.

Events like the murder of Kitty Genovese in 1964—in which false reports claimed 37 witnesses stood by and did nothing as Genovese was stabbed repeatedly—only served to intensify the worry. Despite the misinformation, media discussed the case widely as emblematic of rampant urban moral decay. A host of science fiction works—films like Soylent Green , comics like 2000 AD —played on Calhoun’s ideas and those of his contemporaries . For example, Soylent Green ’s vision of a dystopic future was set in a world maligned by pollution, poverty and overpopulation.

Now, interpretations of Calhoun’s work have changed. Inglis-Arkell explains that the main problem of the habitats he created wasn’t really a lack of space. Rather, it seems likely that Universe 25’s design enabled aggressive mice to stake out prime territory and guard the pens for a limited number of mice, leading to overcrowding in the rest of the world.

However we interpret Calhoun’s experiments, though, we can take comfort in the fact that humans are not rodents. Follow-up experiments by other researchers, which looked at human subjects, found that crowded conditions didn’t necessarily lead to negative outcomes like stress, aggression or discomfort.

“Rats may suffer from crowding,” medical historian Edmund Ramsden told the NIH Record ’s Carla Garnett in 2008, “human beings can cope.”

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Maris Fessenden | | READ MORE

Maris Fessenden is a freelance science writer and artist who appreciates small things and wide open spaces.

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Rudy Molinek is  Smithsonian  magazine's 2024 AAAS Mass Media Fellow.

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While Some Unethical, These 4 Social Experiments Helped Explain Human Behavior

How have we learned about human behavior some studies caused a baby to fear animals — and other experiments helped us explore human nature..

From the CIA’s secret mind control program, MK Ultra, to the stuttering “Monster” study, American researchers have a long history of engaging in human experiments. The studies have helped us better understand ourselves and why we do certain things.

These four experiments did just this and helped us better understand human behavior. However, some of them would be considered unethical today due to either lack of informed consent or the mental and/or emotional damage they caused.

1. Cognitive Dissonance Experiment

After proposing the concept of cognitive dissonance , psychologist Leon Festinger created an experiment to test his theory that was also known as the boring experiment. 

Participants were paid either $1 or $20 to engage in mundane tasks, including turning pegs on a board and moving spools on and off a tray. Despite the boring nature of the activities, they were asked to tell the next participant that it was interesting and fun.

The people who were paid $20 felt more justified lying to others because they were better compensated — and they experienced less cognitive dissonance . Participants who were paid $1 felt greater cognitive dissonance due to their inability to rationalize lying.

In an attempt to reconcile their dissonance, they convinced themselves that the tasks were actually enjoyable.

2. The Little Albert Experiment  

In 1920, psychologist John. B. Watson and graduate student (and future wife) Rosalie Rayner wanted to see if they could produce a response in humans using classical conditioning — the way Pavlov did with dogs.  

They decided to expose a 9-month-old baby, whom they called Albert, to a white rat. At first, the baby displayed no fear and played with the rat. To startle Albert, Watson and Rayner would then make a loud noise by hitting a steel bar with a hammer. 

Each time they made the loud sound while Albert was playing with the rat, he became frightened, started crying, and crawled away from the rat. He had become classically conditioned to fear the rat because he associated it with something negative. He then developed stimulus generalization, where he feared other furry white objects — including a rabbit, white coat, and a Santa mask. 

3. Stanford Prison Experiment

In 1971, Stanford psychologist Philip Zimbardo designed a study to examine societal roles and situational power — through an experiment that recreated prison conditions. 

Zimbardo created a mock prison in a building on Stanford’s campus. He assigned study participants to be either guards or prisoners. Prisoners were given numbers instead of names, had a chain attached to one leg, and were dressed in smocks and stocking caps.

Those assigned to the role of a guard quickly conformed to their new position of power. They became hostile and aggressive toward the prisoners, subjecting them to psychological and verbal abuse — despite never having previously demonstrated such attitudes or behavior. The experiment was slated to last two weeks but needed to be ended after only six days. 

4. The Facial Expression Experiment

In 1924, psychology graduate student Carney Landis wanted to study how people’s emotions were reflected in their facial expressions, exploring whether certain emotions caused the same facial expressions in everyone.

Landis marked participants’ faces with black lines to study the movement of their facial muscles as they reacted. At first, he had them do innocuous tasks, such as listening to jazz music or smelling ammonia. 

As Landis grew frustrated that their responses weren’t strong enough, he had participants engage in increasingly shocking acts, such as sticking their hands into a bucket with live frogs in it. Eventually, Landis instructed participants to decapitate a live mouse. If they refused, he decapitated the mouse himself to elicit a strong reaction from them.

Read More: 5 Unethical Medical Experiments Brought Out of the Shadows of History

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Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:

Advance Research Journal of Social Science . Cognitive dissonance: its role in decision making

New Scientist. How a baby was trained to fear

Stanford Prison Experiment. Philip G. Zimbardo

Incarceration . The dirty work of the Stanford Prison Experiment: Re-reading the dramaturgy of coercion

Journal of Experimental Psychology. Studies of emotional reactions. I. 'A preliminary study of facial expression."

The American Journal of Psychology. Carney Landis: 1897-1962

Allison Futterman is a Charlotte, N.C.-based writer whose science, history, and medical/health writing has appeared on a variety of platforms and in regional and national publications. These include Charlotte, People, Our State, and Philanthropy magazines, among others. She has a BA in communications and a MS in criminal justice.

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Hippos don’t fly – but the massive animals can get airborne

Professor of Evolutionary Biomechanics, Royal Veterinary College

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John R. Hutchinson does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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In 1872 Leland Stanford, the founder of California’s Stanford University, hired an eccentric inventor named Eadweard Muybridge to help resolve a supposed (but undocumented) bet: did a trotting horse’s feet leave the ground with all four feet or not?

Muybridge was a skilled photographer and managed to get blurry snapshots of an “airborne” horse in mid-trot – an example of how the naked eye alone can’t capture fast, subtle motions. He went on, alongside others, to establish what became cinematography . He also continued to capture images of many animals moving, trying to catch them airborne. Of another large animal, the hippo (which he did not photograph) Muybridge wrote :

On dry land it is hardly probable that its fastest gait can be other than the amble [meaning fast but still four-beat, lateral sequence]; possibly a trot, but with a brief period, if any, of non-support.

Was he right? As a scientist whose research partly focuses on how giant land animals like rhinos, elephants, and giraffes move and how gravity uniquely constrains how athletic they can be on land, I’ve long wondered how hippos move on land.

Most people probably think of hippos in terms of their activities in the water, where they do spend much of their time. But they are amphibious animals that spend about one-third of their time on land. At giant sizes (typically around 1400 kg) similar to those of young elephants, hippos should be ponderous and slow on land, especially as they must also be adapted for life in the water and look so bulky. But what seems likely and what is true are not always the same. That’s where the science comes in, to address questions with evidence. We know hippos don’t fly; they have no wings and are too big; but what can they truly achieve under gravity’s hefty pull?

In a recent study , we showed that hippos trot – but at fast speeds they can become airborne with all four feet off the ground at once. This is remarkable because now we know that hippos are one of the largest animals that still can get airborne at fast speeds and yet they are also adapted for a semi-aquatic lifestyle.

A simple experiment

Studying the existing literature about hippo locomotion, I found it wasn’t clear what range of gaits or sequence of footfalls hippos used.

Some studies said they used a “lateral sequence” walking pattern – a “four-beat” gait, contacting the ground with left hind, then left fore, then right hind, then right fore feet.

Others stated that hippos only used a “trotting” pattern even at slower speeds. Here trotting doesn’t mean moving at a moderate speed like a jog. In scientific analysis of locomotion, much as in other areas such as equestrian sport , a trot is a “two-beat” gait in which diagonal limbs move in near-unison, with left hind and right front feet contacting the ground, followed by right hind and left front feet about half of a footfall cycle (“stride”) apart.

Few scientific studies had even considered what hippos do when they move quickly on land. There were some observations that, at least at moderate speeds, hippos trotted.

So I designed a very simple experiment, analogous to what Muybridge did but today a mundane activity: taking digital videos of hippos moving at a range of speeds.

I sent my undergraduate veterinary student, Emily Pringle, to Flamingo Land Resort in North Yorkshire in the UK, armed with basic GoPro cameras, to capture videos of their two adult hippos.

She noted during the two days of intermittent filming that the hippos were slow; just walking. It wasn’t a surprise. Not only did the hippos not spend much time on land (and were out of sight in their barn at night), but there was no way to motivate them to move quickly – they live a safe life.

There was a second part to our plan. The internet is full of videos of wildlife, so we searched Youtube and other websites for more videos of hippos moving at a range of speeds on land, to “bulk up” our data sample. This helped to put our video of the two zoo hippos into a broader context. We hoped to find some footage of hippos moving as quickly as they could, under more motivated (probably wild) conditions.

Video evidence

We collected 169 strides from 46 video clips of 32 hippos. Most of it was slow walking, but all of these walking strides involving trotting patterns. It’s clear that hippos prefer to trot rather than using a four-beat lateral sequence pattern, even at slow speeds.

The videos of wild African hippos, and a couple from zoos, contained the most exciting finding.

About 14 of our 46 hippo videos showed at least brief periods of “non-support”, as Muybridge termed it – becoming airborne with all four feet off the ground.

The fastest sequences showed hippos getting airborne for around 0.3 seconds. That might seem really brief but it’s longer than a single foot might be on the ground (as little as 0.2 seconds). Furthermore, the nervous system of a big animal like a hippo would involve lengthy delays in response to a stumble, so those airborne periods could be risky.

Our findings emphasise how odd hippos’ locomotion is on land. Unlike most other mammals, especially larger ones, they just trot, from slow to fast speeds. We weren’t able to measure precisely how fast hippos can move, but I hypothesise that they’re probably not much faster than elephants, which I’ve shown before to move at up to 25 kph (with a lateral sequence “amble”, never airborne).

Their ability to get even briefly airborne means that hippos are relatively more athletic than elephants, but still less athletic than white rhinos, which can be as big as a hippo yet can gallop and thus be airborne, and probably faster than hippos. This variety of locomotor abilities, expanded by other very large animals that I’ve studied such as giraffes , and even extinct dinosaurs , shows two general patterns.

First, even at giant sizes over 1000 kg, there still remains a variety of athletic abilities that might be usable , such as moving faster than a slow walk, or even going airborne.

Yet second, at such sizes, inevitably there is a decline in maximal speed . As size increases, sooner or later some athletic abilities such as becoming airborne must be sacrificed, in return for the many benefits of giant size.

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Harris Chooses Walz

A guide to the career, politics and sudden stardom of gov. tim walz of minnesota, now vice president kamala harris’s running mate..

Hosted by Michael Barbaro

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Earlier this summer, few Democrats could have identified Gov. Tim Walz of Minnesota.

But, in a matter of weeks, Mr. Walz has garnered an enthusiastic following in his party, particularly among the liberals who cheer on his progressive policies. On Tuesday, Vice President Kamala Harris named him as her running mate. Ernesto Londoño, who reports for The Times from Minnesota, walks us through Mr. Walz’s career, politics and sudden stardom.

On today’s episode

Ernesto Londoño , a reporter for The Times based in Minnesota, covering news in the Midwest.

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Who is Tim Walz , Kamala Harris’s running mate?

Mr. Walz has faced criticism for his response to the George Floyd protests.

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We aim to make transcripts available the next workday after an episode’s publication. You can find them at the top of the page.

The Daily is made by Rachel Quester, Lynsea Garrison, Clare Toeniskoetter, Paige Cowett, Michael Simon Johnson, Brad Fisher, Chris Wood, Jessica Cheung, Stella Tan, Alexandra Leigh Young, Lisa Chow, Eric Krupke, Marc Georges, Luke Vander Ploeg, M.J. Davis Lin, Dan Powell, Sydney Harper, Michael Benoist, Liz O. Baylen, Asthaa Chaturvedi, Rachelle Bonja, Diana Nguyen, Marion Lozano, Corey Schreppel, Rob Szypko, Elisheba Ittoop, Mooj Zadie, Patricia Willens, Rowan Niemisto, Jody Becker, Rikki Novetsky, Nina Feldman, Will Reid, Carlos Prieto, Ben Calhoun, Susan Lee, Lexie Diao, Mary Wilson, Alex Stern, Sophia Lanman, Shannon Lin, Diane Wong, Devon Taylor, Alyssa Moxley, Olivia Natt, Daniel Ramirez and Brendan Klinkenberg.

Our theme music is by Jim Brunberg and Ben Landsverk of Wonderly. Special thanks to Sam Dolnick, Paula Szuchman, Lisa Tobin, Larissa Anderson, Julia Simon, Sofia Milan, Mahima Chablani, Elizabeth Davis-Moorer, Jeffrey Miranda, Maddy Masiello, Isabella Anderson, Nina Lassam and Nick Pitman.

An earlier version of this episode misstated the subject that Walz’s wife taught. She taught English, not Social Studies.

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